α-乳白蛋白错误折叠产物诱导肿瘤细胞凋亡机制研究
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摘要
生物体内的各种功能都是通过蛋白质来行使的,而功能的行使以相应的结构为基础。因此,研究蛋白质结构与功能的关系,有助于我们了解复杂的生命现象。多种人类疾病都和蛋白质错误折叠以及聚集有关。在体内,聚集可能是蛋白质在正常或压力条件下躲过了分子伴侣和蛋白酶体的质量控制监控而造成的失控结果,也有可能执行有益的生物学功能。研究表明,不只疾病相关蛋白质,非致病蛋白质同样能够形成淀粉样纤维,而且也具有细胞毒性。α-乳白蛋白是研究蛋白质折叠和错误折叠的一个经典模型蛋白。它是溶菌酶家族的成员,虽然功能不同,但三级结构与溶菌酶十分相似。该蛋白能够与多种脂肪酸结合。去钙离子的α-乳白蛋白在一定条件下部分去折叠后,能与油酸结合,形成一种能特异性诱导肿瘤细胞凋亡的复合物HAMLET(humanα-lactalbumin made lethal to tumor cells).
我们使用荧光相图和远紫外CD相图对α-乳白蛋白酸变性的过程进行了分析。酸诱导α-乳白蛋白去折叠过程中存在两个中间态,一个是pH 3.0附近的熔球态,另外一个中间态处于pH 4.0-4.5之间。等温滴定量热实验发现α-乳白蛋白在pH 4.3条件下变性时放热明显,可能存在自身聚集现象。我们使用紫外吸收光谱等方法研究了油酸对部分去折叠的人源及牛源α-乳白蛋白的影响。结果表明,pH 4.04.5条件下油酸能够诱导α-乳白蛋白中间体形成聚集体。该聚集体在其生成的pH值环境下完全不溶,但在37℃中性条件下能够重新溶解。我们使用等温滴定量热法检测了中等酸度条件下牛源α-乳白蛋白与油酸的相互作用,得到两者的结合常数约为1×105M-1。细胞毒性实验表明,油酸诱导两种α-乳白蛋白形成的聚集体对人肺癌细胞A549及人白血病细胞HL60都具有显著的的毒性。白血病细胞对于该聚集更为敏感。以上的研究结果有助于我们进一步探索HAMLET形成的分子机制。
我们使用紫外吸收光谱等方法研究了三种脂肪酸对部分去折叠的脱辅基α-乳白蛋白的影响。结果表明,对于处于pH4.0-4.5条件下的牛α-乳白蛋白折叠中间体,两种不饱和脂肪酸(油酸和亚油酸)和一种饱和脂肪酸(硬脂酸),均能够以时间依赖和浓度依赖的方式诱导其形成无定形的非纤维聚集体。该聚集体在37℃中性条件下能够重新溶解。我们使用内源荧光光谱、ANS结合、远紫外圆二色光谱以及飞行时间质谱对其进行了分析。结果表明,该聚集体在重新溶解后,结构特征类似于HAMLET/BAMLET。细胞毒性实验表明,油酸和亚油酸诱导α-乳白蛋白形成的聚集体对人肺癌细胞A549具有显著的、浓度依赖的毒性,而硬脂酸诱导的聚集则没有对该肿瘤细胞表现出明显毒性。此外,两种不饱和脂肪酸诱导α-乳白蛋白形成的聚集体能够诱导A549凋亡,因此这种聚集体有被开发成抗肿瘤药物的潜在价值。以上研究结果有助于了解脂肪酸导致的α-乳白蛋白的寡聚化现象以及HAMLET/BAMLET形成的分子机制。折叠构象的改变有可能使同一条蛋白质多肽链能够行使不同的生物学功能,深化了我们对蛋白质结构与功能关系的认识。
Proteins are the executives of different biological functions in vivo. The functions of proteins are based on their structure. Therefore, to research the relationship between structure and function will help us better understand various complex phenomena in lives,α-lactalbumin is a member of lysozyme family and has similar structure to lysozymes. It can bind to fatty acids and novel functions were found. It was reported that complex ofα-lactalbumin and oleic acid named after HAMLET (humanα-lactalbumin made lethal to tumor cells) induces apoptosis in tumor cells but spares healthy cell. In our research, we take both bovineα-lactalbumin (apo-BLA) and humanα-lactalbumin (holo-HLA) as examples to investigate the effects of oleic acid onα-lactalbumin in various pH. The results from "phase diagram" method indicate that there are two intermediates in the conformational transition of apo-BLA induced by acid. One intermediate populated at pH 3.0 while the other accumulates at pH 4.0-4.5. The interaction ofα-lactalbumin and oleic acid was measured by ITC and a binding constant of about 1×10-5 M-1 was observed. The binding of oleic acid to apo-BLA is driven entirely by large favorable entropy increases but with unfavorable enthalpy increases for the first and the third sequential binding sites of the protein. Cell viability experiments indicate the aggregates of either BLA or HLA induced by oleic acid show significant dose-dependent cytotoxicity to human lung tumor cells of A549 and human promyelocytic leukemia cells of HL60.
The effects of three fatty acids on cytotoxic aggregate formation of Ca2+-depleted bovineα-lactalbumin (apo-BLA) have been studied by UV absorbance spectroscopy and transmission electron microscopy. The experimental results demonstrate that two unsaturated fatty acids, oleic acid and linoleic acid, and one saturated fatty acid, stearic acid, induce the intermediate of apo-BLA at pH 4.0-4.5 to form amorphous aggregates in time- and concentration-dependent manners. These aggregates are dissolved under physiological conditions at 37℃and further characterized by fluorescence spectroscopy, circular dichroism and time-of-flight mass spectrometry. Our data here indicate that the structural characteristics of these aggregates are similar to those of HAMLET/BAMLET (human/bovineα-lactalbumin made lethal to tumor cells), a complex of the partially unfoldedα-lactalbumin with oleic acid. Cell viability experiments indicate the aggregates of apo-BLA induced by oleic acid and linoleic acid show significant dose-dependent cytotoxicity to human lung tumor cells of A549 but those induced by stearic acid have no toxicity to tumor cells. Furthermore, the cytotoxic aggregates of apo-BLA induced by both unsaturated fatty acids induce apoptosis of human lung cancer cell line A549, suggesting that such cytotoxic aggregates of apo-BLA could be potential antitumor drugs. The present study provides insight into the mechanism of fatty acid-dependent oligomerization and cytotoxicity ofα-lactalbumin, and will be helpful to the understanding of the molecular mechanism of HAMLET/BAMLET formation.
我们使用荧光相图和远紫外CD相图对α-乳白蛋白酸变性的过程进行了分析。酸诱导α-乳白蛋白去折叠过程中存在两个中间态,一个是pH 3.0附近的熔球态,另外一个中间态处于pH 4.0-4.5之间。等温滴定量热实验发现α-乳白蛋白在pH 4.3条件下变性时放热明显,可能存在自身聚集现象。我们使用紫外吸收光谱等方法研究了油酸对部分去折叠的人源及牛源α-乳白蛋白的影响。结果表明,pH 4.04.5条件下油酸能够诱导α-乳白蛋白中间体形成聚集体。该聚集体在其生成的pH值环境下完全不溶,但在37℃中性条件下能够重新溶解。我们使用等温滴定量热法检测了中等酸度条件下牛源α-乳白蛋白与油酸的相互作用,得到两者的结合常数约为1×105M-1。细胞毒性实验表明,油酸诱导两种α-乳白蛋白形成的聚集体对人肺癌细胞A549及人白血病细胞HL60都具有显著的的毒性。白血病细胞对于该聚集更为敏感。以上的研究结果有助于我们进一步探索HAMLET形成的分子机制。
我们使用紫外吸收光谱等方法研究了三种脂肪酸对部分去折叠的脱辅基α-乳白蛋白的影响。结果表明,对于处于pH4.0-4.5条件下的牛α-乳白蛋白折叠中间体,两种不饱和脂肪酸(油酸和亚油酸)和一种饱和脂肪酸(硬脂酸),均能够以时间依赖和浓度依赖的方式诱导其形成无定形的非纤维聚集体。该聚集体在37℃中性条件下能够重新溶解。我们使用内源荧光光谱、ANS结合、远紫外圆二色光谱以及飞行时间质谱对其进行了分析。结果表明,该聚集体在重新溶解后,结构特征类似于HAMLET/BAMLET。细胞毒性实验表明,油酸和亚油酸诱导α-乳白蛋白形成的聚集体对人肺癌细胞A549具有显著的、浓度依赖的毒性,而硬脂酸诱导的聚集则没有对该肿瘤细胞表现出明显毒性。此外,两种不饱和脂肪酸诱导α-乳白蛋白形成的聚集体能够诱导A549凋亡,因此这种聚集体有被开发成抗肿瘤药物的潜在价值。以上研究结果有助于了解脂肪酸导致的α-乳白蛋白的寡聚化现象以及HAMLET/BAMLET形成的分子机制。折叠构象的改变有可能使同一条蛋白质多肽链能够行使不同的生物学功能,深化了我们对蛋白质结构与功能关系的认识。
Proteins are the executives of different biological functions in vivo. The functions of proteins are based on their structure. Therefore, to research the relationship between structure and function will help us better understand various complex phenomena in lives,α-lactalbumin is a member of lysozyme family and has similar structure to lysozymes. It can bind to fatty acids and novel functions were found. It was reported that complex ofα-lactalbumin and oleic acid named after HAMLET (humanα-lactalbumin made lethal to tumor cells) induces apoptosis in tumor cells but spares healthy cell. In our research, we take both bovineα-lactalbumin (apo-BLA) and humanα-lactalbumin (holo-HLA) as examples to investigate the effects of oleic acid onα-lactalbumin in various pH. The results from "phase diagram" method indicate that there are two intermediates in the conformational transition of apo-BLA induced by acid. One intermediate populated at pH 3.0 while the other accumulates at pH 4.0-4.5. The interaction ofα-lactalbumin and oleic acid was measured by ITC and a binding constant of about 1×10-5 M-1 was observed. The binding of oleic acid to apo-BLA is driven entirely by large favorable entropy increases but with unfavorable enthalpy increases for the first and the third sequential binding sites of the protein. Cell viability experiments indicate the aggregates of either BLA or HLA induced by oleic acid show significant dose-dependent cytotoxicity to human lung tumor cells of A549 and human promyelocytic leukemia cells of HL60.
The effects of three fatty acids on cytotoxic aggregate formation of Ca2+-depleted bovineα-lactalbumin (apo-BLA) have been studied by UV absorbance spectroscopy and transmission electron microscopy. The experimental results demonstrate that two unsaturated fatty acids, oleic acid and linoleic acid, and one saturated fatty acid, stearic acid, induce the intermediate of apo-BLA at pH 4.0-4.5 to form amorphous aggregates in time- and concentration-dependent manners. These aggregates are dissolved under physiological conditions at 37℃and further characterized by fluorescence spectroscopy, circular dichroism and time-of-flight mass spectrometry. Our data here indicate that the structural characteristics of these aggregates are similar to those of HAMLET/BAMLET (human/bovineα-lactalbumin made lethal to tumor cells), a complex of the partially unfoldedα-lactalbumin with oleic acid. Cell viability experiments indicate the aggregates of apo-BLA induced by oleic acid and linoleic acid show significant dose-dependent cytotoxicity to human lung tumor cells of A549 but those induced by stearic acid have no toxicity to tumor cells. Furthermore, the cytotoxic aggregates of apo-BLA induced by both unsaturated fatty acids induce apoptosis of human lung cancer cell line A549, suggesting that such cytotoxic aggregates of apo-BLA could be potential antitumor drugs. The present study provides insight into the mechanism of fatty acid-dependent oligomerization and cytotoxicity ofα-lactalbumin, and will be helpful to the understanding of the molecular mechanism of HAMLET/BAMLET formation.
引文
冯佑民蛋白质折叠.生命的化学1995,15(2),4-7.
梁毅结构生物学.(2005)科学出版社第一版193-236.
斯佩克特,戈德曼,莱因万德,黄培堂细胞实验指南.(2001)科学出版社.
王志珍蛋白质折叠和分子伴侣.生物学通报2004,39(5),1-6.
赵南明,周海梦生物物理学.(2004)高等教育出版社.
邹承鲁第二遗传密码.科学通报2000,45,1681-1687.
邹承鲁结构生物学的时代已经开始.科技导报1995,04(7),7-11.
Acharya, K. R., Ren, J. S., Stuart, D. I., Phillips, D. C.& Fenna, R. E. Crystal structure of human a-lactalbumin at 1.7 A resolution. J. Mol. Biol.1991,221, 571-581.
Acharya, K. R., Stuart, D. I., Phillips, D. C., McKenzie, H. A.& Teahan, C. G. Models of the three-dimensional structures of echidna, horse, and pigeon lysozymes: calcium-binding lysozymes and their relationship with a-lactalbumins. J. Protein Chem.1994,13,569-584.
Aits, S., Gustafsson, L., Hallgren,O., Brest, P., Gustafsson, M., Trulsson, M., Mossberg, A.K., Simon, H.U., Mograbi, B., Svanborg, C. HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death. Int J. Cancer.124,1008-1019.
Anfinsen, C. B., Haber, E., Sela, M.& White, Jr. F. H. The kinetics of formation of native ribonuclease during oxidation of the reduced polypeptide chain. Proc. Natl. Acad. Sci. U. S. A.1961,47,1309-1314.
Aramini, J. M., Hiraoki, T., Grace, M. R., Swaddle, T. W., Chiancone, E.& Vogel, H. J. NMR and stopped-flow studies of metal ion binding to a-lactalbumins. Biochim. Biophys. Acta 1996,1293,72-82.
Barbana, C., Perez, M. D., Sanchez, L., Dalgalarrondo, M., Chobert, J. M., Haertle, T. & Calvo, M. Interaction of bovine a-lactalbumin with fatty acids as determined by partition equilibrium and fluorescence spectroscopy. Int. Dairy J.2006,16,18-25.
Bates, S.& Vousden, K. H. Mechanisms of p53-mediated apoptosis. Cell Mol. Life Sci.1999,55,28-37.
Bhattacharjee, R. N., Park, K. S., Kumagai, Y., Okada, K., Yamamoto, M., Uematsu, S., Matsui, K., Kumar, H., Kawai, T., Iida, T.,Akira, S. VP1686, a Vibrio type Ⅲ secretion protein, induces toll-like receptor-independent apoptosis in macrophage through NF-κB Inhibition. J. Biol. Chem.2006,281,36897-36904.
Bomhoff, G., Sloan, K., McLain, C., Gogol, E. P.& Fisher, M. T. The effects of the flavonoid baicalein and osmolytes on the Mg2+ accelerated aggregation/fibrillation of carboxymethylated bovine 1SS-α-lactalbumin. Arch. Biochem. Biophys.2006,453, 75-86.
Booth, D. R., Sunde, M., Bellotti, V., Robinson, C. V., Hutchinson, W. L., Fraser, P. E., Hawkins, P. N., Dobson, C. M., Radford, S. E., Blake, C. C.& Pepys, M. B. Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis. Nature 1997,385,787-793.
Bucciantini, M., Calloni, G., Chiti, F., Formigli, L., Nosi, D., Dobson, C. M.& Stefani, M.. Prefibrillar amyloid protein aggregates share common features of cytotoxicity. J. Biol. Chem.2004,279,31374-31382.
Bucciantini, M., Giannoni, E., Chiti, F., Baroni, F., Formigli, L., Zurdo, J., Taddei, N., Ramponi,G., Dobson, C. M.& Stefani, M. Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 2002,416,507-511.
Bushmarina, N. A., Kuznetsova, I. M., Biktashev, A. G., Turoverov, K. K., Uversky, V. N. Partially folded conformations in the folding pathway of bovine carbonic anhydrase Ⅱ:a fluorescence spectroscopic analysis. Chembiochem 2001,2(11): 813-821.
Calamai, M., Canale, C., Relini, A., Stefani, M., Chiti, F.& Dobson, C. M. Reversal of protein aggregation provides evidence for multiple aggregated States. J. Mol. Biol. 2005,346,603-616.
Calamai, M., Chiti, F.& Dobson, C. M. Amyloid fibril formation can proceed from different conformations of a partially unfolded protein. Biophys. J.2005,89, 4201-4210.
Carulla, N., Caddy, G L., Hall, D. R., Zurdo, J., Gairi, M., Feliz, M., Giralt, E., Robinson, C. V.& Dobson, C. M. Molecular recycling within amyloid fibrils. Nature 2005,436,554-558.
Cawthern, K. M., Permyakov, E., Berliner, L. J. Membrane-bound states of α-lactalbumin:implications for the protein stability and conformation. Protein Sci.1996,5,1394-1405.
Cawthern, K. M., Narayan, M., Chaudhuri, D., Permyakov, E. A., Berliner, L. J., Interactions of a-lactalbumin with fatty acids and spin label analogs. J. Biol. Chem. 1997,272,30812-30816.
Chandra, N., Brew, K.& Acharya, K. R. Structural evidence for the presence of a secondary calcium binding site in human a-lactalbumin. Biochemistry 1998,37, 4767-4772.
Chiti, F., Bucciantini, M., Capanni, C, Taddei, N., Dobson, C. M.& Stefani, M. Solution conditions can promote formation of either amyloid protofilaments or mature fibrils from the HypF N-terminal domain. Protein Sci.2001,10,2541-2547.
Chiti, F., De Lorenzi, E., Grossi, S., Mangione, P., Giorgetti, S., Caccialanza, G., Dobson, C. M., Merlini, G., Ramponi, G.& Bellotti, V. A partially structured species of beta 2-microglobulin is significantly populated under physiological conditions and involved in fibrillogenesis. J. Biol. Chem.2001,276,46714-21.
Chiti, F.& Dobson, C. M. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem.2006,75,333-366.
Chiti, F., Mangione, P., Andreola, A., Giorgetti, S., Stefani, M., Dobson, C. M., Bellotti, V.& Taddei, N. Detection of two partially structured species in the folding process of the amyloidogenic protein beta 2-microglobulin. J. Mol. Biol.2001,307, 379-391.
Chiti, F., Stefani, M., Taddei, N., Ramponi, G.& Dobson, C. M. Rationalization of the effects of mutations on peptide and protein aggregation rates. Nature 2003,424, 805-808.
Chiti, F., Taddei, N., Bucciantini, M., White, P., Ramponi, G.& Dobson, C. M. Mutational analysis of the propensity for amyloid formation by a globular protein. Embo J.2000,19,1441-1449.
Cistola, D. P., Hamilton, J. A., Jackson, D.& Small, D. M. Ionization and phase behavior of fatty acids in water:application of the Gibbs phase rule. Biochemistry 1988,27,1881-1888.
Darzynkiewicz, Z., Gong, J. P., Traganos, F. Expression of cell-cycle specific proteins cyclins as a marker of the cell-cycle position, independent of DNA content, in:Z. Darzynkiewicz, P. J. Robinson, H. A. Crissman (Eds.), Flow Cytometry,2nd Edition, Academic Press, San Diego, CA,1994.
De Felice, F. G., Vieira, M. N., Meirelles, M. N., Morozova-Roche, L. A., Dobson, C. M.& Ferreira, S. T. Formation of amyloid aggregates from human lysozyme and its disease-associated variants using hydrostatic pressure. Faseb J.2004,18,1099-1101. de Laureto, P. P., Frare, E., Gottardo, R., Van Dael, H.& Fontana, A. Partly folded states of members of the lysozyme/lactalbumin superfamily:a comparative study by circular dichroism spectroscopy and limited proteolysis. Protein Sci.2002,11, 2932-2946.
de Laureto, P. P., Frare, E., Battaglia, F., Mossuto, M. F., Uversky, V. N.& Fontana, A. Protein dissection enhances the amyloidogenic properties of α-lactalbumin. FEBS J.2005,272,2176-2188.
Dirix, C., Meersman, F., MacPhee, C. E., Dobson, C. M.& Heremans, K. High hydrostatic pressure dissociates early aggregates of TTR105-115, but not the mature amyloid fibrils. J. Mol. Biol.2005,347,903-909.
Dobson, C. M. Experimental investigation of protein folding and misfolding. Methods 2004,34,4-14.
Dobson, C. M. Protein chemistry. In the footsteps of alchemists. Science 2004,304, 1259-62.
Dobson, C. M. Protein misfolding, evolution and disease. Trends Biochem. Sci.1999, 24,329-332.
Dobson, C. M. Principles of protein folding, misfolding and aggregation. Semin. Cell Dev. Biol.2004,15,3-16.
Dobson, C. M. Structural biology:prying into prions. Nature 2005,435,747-749.
Dobson, C. M.& Ellis, R. J. Protein folding and misfolding inside and outside the cell. Embo J.1998,17,5251-5254.
Dolgikh, D. A., Abaturov, L. V., Bolotinna, I. A., Brazhnikov, E. V., Bychkova, V. E., .Gilmanshin, R. I., Lebedev, Yu.O., Semisotnov, G. V., Tiktopulo, E. I.& Ptitsyn, O. B. Compact state of a protein molecule with pronounced small-scale mobility:bovine a-lactalbumin. Eur. Biophys. J.1985,13,109-120.
Dolgikh, D. A., Gilmanshin, R. I., Brazhnikov, E. V., Bychkova, V. E., Semisotnov, G. V., Venyaminov, S.& Ptitsyn, O. B. α-Lactalbumin:compact state with fluctuating tertiary structure? FEBS Lett.1981,136,311-315.
DuBay, K. F., Pawar, A. P., Chiti, F., Zurdo, J., Dobson, C. M.& Vendruscolo, M. Prediction of the absolute aggregation rates of amyloidogenic polypeptide chains. J. Mol. Biol.2004,341,1317-1326.
van, Duijn, E., Bakkes, P. J., Heeren, R. M., van, den, Heuvel, R. H., van, Heerikhuizen, H., van, der, Vies, S. M.,. Heck, A.J. Monitoring macromolecular complexes-involved in the chaperonin-assisted protein folding cycle by mass spectrometry.Nat.Methods.2005,2,371-376.
Dumoulin, M., Canet, D., Last, A. M., Pardon, E., Archer, D. B., Muyldermans, S., Wyns, L., Matagne, A., Robinson, C. V., Redfield, C.& Dobson, C. M. Reduced global cooperativity is a common feature underlying the amyloidogenicity of pathogenic lysozyme mutations. J. Mol. Biol.2005,346,773-788.
Duringer, C., Hamiche, A., Gustafsson, L., Kimura, H.& Svanborg, C. HAMLET interacts with histones and chromatin in tumor cell nuclei. J. Biol. Chem.2003,278, 42131-42135.
Eftink, M. R.& Ghiron, C. A. Fluorescence quenching studies with proteins. Anal. Biochem.1981,114,199-227.
Ellis, R. J.& Hartl, F. U. Principles of protein folding in the cellular environment. Gurr.Opin. Struct. Biol.1999,9,102-110.
Engebraaten, O., Hjortland, G. O., Hirschberg, H.& Fodstad, O. Growth of precultured human glioma specimens in nude rat brain. J. Neurosurg.1999,90, 125-132.
Fandrich, M., Fletcher, M. A.& Dobson, C.M. Amyloid fibrils from muscle myoglobin. Nature 2001,410,165-166.
Fandrich, M.& Dobson, C. M. The behaviour of polyamino acids reveals an inverse side chain effect in amyloid structure formation. Embo J.2002,21,5682-5690.
Fast, J., Mossberg, A. K., Nilsson, H., Svanborg, C., Akke, M.& Linse, S. Compact oleic acid in HAMLET. FEBS Lett.2005,579,6095-6100.
Fischer, W., Gustafsson, L., Mossberg, A. K., Gronli, J., Mork, S., Bjerkvig, R.& Svanborg, C. Human a-lactalbumin made lethal to tumor cells (HAMLET) kills human glioblastoma cells in brain xenografts by an apoptosis-like mechanism and prolongs survival. Cancer Res.2004,64,2105-2112.
Frare, E., Polverino De Laureto, P., Zurdo, J., Dobson, C. M.& Fontana, A. A highly amyloidogenic region of hen lysozyme. J.Mol. Biol.2004,340,1153-1165.
Gharibyan, A. L., Zamotin, V., Yanamandra, K., Moskaleva, O. S., Margulis, B. A., Kostanyan, I. A., Morozova-Roche, L. A. Lysozyme amyloid oligomers and fibrils induce cellular death via different apoptotic/necrotic pathways. J. Mol. Biol.2007,365, 1337-1349.
Goldsbury, C., Kistler, J., Aebi, U., Arvinte, T.& Cooper, G J.. Watching amyloid fibrils grow by time-lapse atomic force microscopy. J. Mol. Biol.1999,285,33-39.
Gosal, W. S., Clark, A. H.& Ross-Murphy, S. B. Fibrillar beta-lactoglobulin gels:Part 1. Fibril formation and structure. Biomacromolecules 2004,5,2408-2419.
Green, D. R.& Kroemer, G The pathophysiology of mitochondrial cell death. Science 2004,50,626-629.
Gundersen, S., Lote, K.& Hannisdal, E. Prognostic factors for glioblastoma multiforme-development of a prognostic index. Acta Oncol.1996,35 (Suppl.8), 123-127.
Gussakovsky, E. E., Haas, E. Two steps in the transition between the native and acid states of bovine a-lactalbumin detected by circular polarization of luminescence: evidence for a premolten globule state? Protein Sci.1995,4,2319-2326.
Gustafsson, L., Hallgren, O., Mossberg, A. K., Pettersson, J., Fischer, W., Aronsson, A. & Svanborg, C. HAMLET kills tumor cells by apoptosis:structure, cellular mechanisms, and therapy. J. Nutr.2005,135,1299-1303.
Gustafsson, L., Leijonhufvud, I., Aronsson, A., Mossberg, A. K.& Svanborg, C. Treatment of skin papillomas with topical a-lactalbumin-oleic acid. N. Engl. J. Med. 2004,350,2663-2672.
Goers, J., Permyakov, S. E., Permyakov, E. A., Uversky, V. N.& Fink, A. L. Conformational prerequisites for a-lactalbumin fibrillation. Biochemistry 2002,41, 12546-12551.
Hakansson, A., Andreasson, J., Zhivotovsky, B., Karpman, D., Orrenius, S.& Svanborg, C. Multimeric α-lactalbumin from human milk induces apoptosis through a direct effect on cell nuclei. Exp. Cell Res.1999,246,451-460.
Hakansson, A., Zhivotovsky, B., Orrenius, S., Sabharwal, H.& Svanborg, C. Apoptosis induced by a human milk protein. Proc. Natl. Acad. Sci. U. S. A.1995,92, 8064-8068.
Hall, D., Hirota, N.& Dobson, C. M. A toy model for predicting the rate of amyloid formation from unfolded protein. J. Mol Biol.2005,351,195-205.
Hallgren, O., Gustafsson, L., Irjala, H., Selivanova, G., Orrenius, S.& Svanborg, C. HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53.Apoptosis 2006,11,221-233.
Halliburton, W.D. The Proteids of Milk. J. Physiol. 1890,11,448-463.
Hamada, D.& Dobson, C.M. A kinetic study of beta-lactoglobulin amyloid fibril formation promoted by urea. Protein Sci.2002,11,2417-2426.
Hamodrakas, S. J., Hoenger, A.& Iconomidou, V. A. Amyloid fibrillogenesis of silkmoth chorion protein peptide-analogues via a liquid-crystalline intermediate phase. J. Struct. Biol.2004,145,226-235.
Harper, J. D.& Lansbury, P. T., Jr. Models of amyloid seeding in Alzheimer's disease and scrapie:mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteins. Annu. Rev. Biochem.1997,66,385-407.
Hartl, F. U. Molecular chaperones in cellular protein folding. Nature 1996,381, 571-580.
Ikeguchi, M., Kuwajima, K., Mitani, M.& Sugai, S. Evidence for identity between the equilibrium unfolding intermediate and a transient folding intermediate:a .comparative study of the folding reactions of α-lactalbumin and lysozyme. Biochemistry 1986,25,6965-6972.
Jaroniec, C. P., MacPhee, C. E., Astrof, N. S., Dobson, C. M.& Griffin, R. G. Molecular conformation of a peptide fragment of transthyretin in an amyloid fibril. Proc. Natl.Acad. Sci. U. S. A.2002,99,16748-16753.
Jaroniec, C. P., MacPhee, C. E., Bajaj, V. S., McMahon, M. T., Dobson, C. M.& Griffin, R. G. High-resolution molecular structure of a peptide in an amyloid fibril determined by magic angle spinning NMR spectroscopy. Proc. Natl.Acad. Sci. U. S. A.2004,101,711-716.
Jeffery, C.J., Moonlighting proteins. Trends Biochem Sci,1994,24,8-11.
Jeffery, C.J., Moonlighting proteins:old proteins learning new tricks. Trends Genet, 2003,19,415-417.
Jimenez, J. L., Nettleton, E. J., Bouchard, M., Robinson, C. V., Dobson, C. M.& Saibil, H. R. The protofilament structure of insulin amyloid fibrils. Proc. Natl.Acad. Sci. U. S. A.2002,99,9196-9201.
Johnson, R. J., Christodoulou, J., Dumoulin, M., Caddy, G. L., Alcocer, M. J., Murtagh, G. J., Kumita, J. R., Larsson, G., Robinson, C. V., Archer, D. B., Luisi, B. & Dobson, C. M. Rationalising lysozyme amyloidosis:insights from the structure and solution dynamics of T70N lysozyme.J. Mol. Biol.2005,352,823-836.
Kammerer, R. A., Kostrewa, D., Zurdo, J., Detken, A., Garcia-Echeverria, C., Green, J. D., Muller, S. A., Meier, B. H., Winkler, F. K., Dobson, C. M.& Steinmetz, M. O. Exploring amyloid formation by a de novo design. Proc. Natl.Acad. Sci. U. S. A. 2004,101,4435-4440.
Katsarou, M. E., Efthimiadou, E. K, Psomas, G, Karaliota, A., Vourloumis, D. Novel copper(Ⅱ) complex of N-propyl-norfloxacin and 1,10-phenanthroline with enhanced antileukemic and DNA nuclease activities. J. Med. Chem.2008,51,470-478.
Kelly, J. W. The environmental dependency of protein folding best explains prion and amyloid diseases. Proc. Natl. Acad Sci. U. S. A.1998,95,930-932.
Kim, Y. J., Nakatomi, R., Akagi, T., Hashikawa, T.& Takahashi, R. Unsaturated fatty acids induce cytotoxic aggregate formation of amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutants. J. Biol. Chem.2005,280,21515-21521.
Kohler, C., Gogvadze, V., Hakansson, A., Svanborg, C., Orrenius, S.& Zhivotovsky, B. A folding variant of human a-lactalbumin induces mitochondrial permeability transition in isolated mitochondria. Eur. J. Biochem.2001,268,186-191.
Kohler, C., Hakansson, A., Svanborg, C., Orrenius, S.& Zhivotovsky, B. Protease activation in apoptosis induced by MAL. Exp. Cell Res.1999,249,260-268.
Konermann, L.& Douglas, D. J. Acid-induced unfolding of cytochrome c at different methanol concentrations:electrospray ionization mass spectrometry specifically monitors changes in the tertiary structure. Biochemistry 1997,36,12296-12302.
Konermann, L.& Douglas, D. J. Equilibrium unfolding of proteins monitored by electrospray ionization mass spectrometry:distinguishing two-state from multi-state transitions. Rapid Commun. Mass Spectrom.1998,12,435-442.
Kostovay Z.& Wolf, D. H. For whom the bell tolls:protein quality control of the endoplasmic reticulum and the ubiquitin-proteasome connection. EMBO. J.2003,22, 2309-2317.
Krebs, M. R., Macphee, C. E., Miller, A. F., Dunlop, I. E., Dobson, C. M.& Donald, A. M. The formation of spherulites by amyloid fibrils of bovine insulin. Proc. Natl. Acad. Sci. U. S. A.2004,101,14420-14424.
Krebs, M. R., Morozova-Roche, L. A., Daniel, K., Robinson, C. V.& Dobson, C. M. Observation of sequence specificity in the seeding of protein amyloid fibrils. Protein Sci.2004,13,1933-1938.
Krebs, M. R., Wilkins, D. K., Chung, E. W., Pitkeathly, M. C., Chamberlain, A. K., Zurdo, J., Robinson, C. V.& Dobson, C. M. Formation and seeding of amyloid fibrils from wild-type hen lysozyme and a peptide fragment from the beta-domain. J. Mol. Biol. 2000,300,541-549.
Kronman, M. J., Andreotti, R.& Vitols, R. Inter- and intramolecular interactions of a-Lactalbumin. Ⅱ. Aggregation reactions at acid pH. Biochemistry 1964,3, 1152-1160.
Kuwajima, K. A folding model of a-lactalbumin deduced from the three-state denaturation mechanism. J. Mol. Biol.1977,114,241-258.
Kuwajima, K., Mitani, M.& Sugai, S. Characterization of the critical state in protein folding. Effects of guanidine hydrochloride and specific Ca2+ binding on the folding kinetics of α-lactalbumin. J. Mol. Biol.1989,206,547-561.
Kuwajima, K. The molten globule state of α-lactalbumin. Faseb. J.1996,10, 102-109.
Kuznetsova, I. M., Stepanenko, O. V., Turoverov, K. K., Zhu, L., Fan, Y. X., Zhou, J. M., Fink, A. L.& Uversky, V. N. Unraveling multistate unfolding of rabbit muscle creatine kinase. Biochim. Biophys. Acta 2002,1596,138-155.
Lala, A. K., Kaul, P. Increased exposure of hydrophobic surface in molten globule state of α-lactalbumin. Fluorescence and hydrophobic photolabeling studies. J. Biol. Chem.1992,267,19914-19918.
Lane, D. P. Cancer. A death in the life of p53. Nature 1993,362,786-787.
Lansbury, P. T., Jr. Evolution of amyloid:what normal protein folding may tell us about fibrillogenesis and disease. Proc. Natl. Acad. Sci. U. S. A.1999,96,3342-3344.
Lehrer, S. S. Solute perturbation of protein fluorescence. The quenching of the tryptophyl fluorescence of model compounds and of lysozyme by iodide ion. Biochemistry 1971,10,3254-3263.
Liang, Y., Du, F., Sanglier, S., Zhou, B. R., Xia, Y, Dorsselaer, A. V., Maechling, C., Kilhoffer, M. C.& Haiech, J. Unfolding of Rabbit Muscle Creatine Kinase Induced by Acid:A study using electrospray ionization mass spectrometry, isothermal titration calorimetry, and fluorescence spectroscopy. J. Biol. Chem.2003,278,30098-30105.
Liang, Y. Applications of isothermal titration calorimetry in protein science. Acta Biochim. Biophys. Sin.2008,40,565-576.
Liang, Y, Huang, G. C., Chen, J.& Zhou, J. M. Microcalorimetric studies on the unfolding of creatine kinase induced by guanidine hydrochloride. Thermochim. Acta 2001,376,123-131.
Lonnerdal, B.& Lien, E. L. Nutritional and physiologic significance of a-lactalbumin in infants. Nutr. Rev.2003,61,295-305.
Lopez De La Paz, M., Goldie, K., Zurdo, J., Lacroix, E., Dobson, C. M., Hoenger, A. & Serrano, L. De novo designed peptide-based amyloid fibrils. Proc. Natl. Acad. Sci. U. S.A:2002,99,16052-16057.
Ma, Z.& Westermark, G. T. Effects of free fatty acid on polymerization of islet amyloid polypeptide (IAPP) in vitro and on amyloid fibril formation in cultivated isolated islets of transgenic mice overexpressing human IAPP. Mol Med.2002,8, 863-868.
MacPhee, C. E.& Dobson, C. M. Chemical dissection and reassembly of amyloid fibrils formed by a peptide fragment of transthyretin. J. Mol. Biol 2000,297, 1203-1215.
Malisauskas, M., Zamotin, V., Jass, J., Noppe, W., Dobson, C. M.& Morozova-Roche, L. A. Amyloid protofilaments from the calcium-binding protein equine lysozyme: formation of ring and linear structures depends on pH and metal ion concentration. J. Mol. Biol.2003,330,879-890.
Malisauskas, M., Ostman, J., Darinskas, A., Zamotin, V., Liutkevicius, E., Lundgren, E., Morozova-Roche, L. A. Does the cytotoxic effect of transient amyloid oligomers from common equine lysozyme in vitro imply innate amyloid toxicity? J. Biol. Chem. 2005,280,6269-6275.
Makhatadze, G. I.& Privalov, P. L. Protein interactions with urea and guanidinium chloride. A calorimetric study. J. Mol. Biol. 1992,226,491-505.
Makhatadze, G I. Thermodynamics of protein interactions with urea and guanidinium hydrochloride. J. Phys.Chem.1999,103,4781-4784.
Marcon, G., Plakoutsi, G., Canale, C., Relini, A., Taddei, N., Dobson, C. M., Ramponi, G & Chiti, F. Amyloid formation from HypF-N under conditions in which the protein is initially in its native state. J. Mol. Biol 2005,347,323-335.
Marek, P., Abedini, A., Song, B., Kanungo, M., Johnson, M. E., Gupta, R., Zaman, W., Wong, S. S.& Raleigh, D. P.. Aromatic Interactions Are Not Required for Amyloid Fibril Formation by Islet Amyloid Polypeptide but Do Influence the Rate of Fibril Formation and Fibril Morphology. Biochemistry 2007,46,3255-3261.
Mastrangelo, I. A., Ahmed, M., Sato, T., Liu, W., Wang, C., Hough, P.& Smith, S. O. High-resolution atomic force microscopy of soluble Abeta42 oligomers. J. Mol. Biol. 2006,358,106-119.
Mathur, G. P., Gupta, N., Mathur, S., Gupta, V., Pradhan, S., Dwivedi, J. N., Tripathi, B. N., Kushwaha, K. P., Sathy, N., Modi, U. J.& et al. Breastfeeding and childhood cancer. Indian Pediatr.1993,30,651-657.
McKenzie, H. A.& White, F. H., Jr., Studies on a trace cell lytic activity associated with α-lactalbumin. Biochem. Int.1987,14,347-356.
Meehan, S., Berry, Y., Luisi, B., Dobson, C. M., Carver, J. A.& MacPhee, C. E. Amyloid fibril formation by lens crystallin proteins and its implications for cataract formation. J. Biol. Chem.2004,279,3413-3419.
Mok, K. H., Pettersson, J., Orrenius, S.& Svanborg, C. HAMLET, protein folding, and tumor cell death. Biochem. Biophys. Res. Commun.2007,354,1-7.
Mosmann, T., Rapid colorimetric assay for cellular growth and survival:application to proliferation and cytotoxicity assays. J. Immunol. Methods.1983,65,55-63.
Munishkina, L. A., Fink, A. L.& Uversky, V. N. Conformational prerequisites for formation of amyloid fibrils from histones. J. Mol. Biol.2004,342,1305-1324.
Naiki, H., Higuchi, K., Hosokawa, M.& Takeda, T. Fluorometric determination of amyloid fibrils in vitro using the fluorescent dye, thioflavin T1. Anal. Biochem.1989, 177,244-249.
Nilsson, M. R.& Dobson, C. M. Chemical modification of insulin in amyloid fibrils. Protein Sci.2003,12,2637-2641.
Nilsson, M. R.& Dobson, C. M. In vitro characterization of lactoferrin aggregation and amyloid formation. Biochemistry 2003,42,375-382.
Ohgushi, M.& Wada, A.'Molten-globule state':a compact form of globular proteins with mobile side-chains. FEBS Lett.1983,14,21-24.
Pellegrini, A., Thomas, U., Bramaz, N., Hunziker, P.& von Fellenberg, R. Isolation and identification of three bactericidal domains in the bovine a-lactalbumin molecule. Biochim. Biophys. Acta 1999,1426,439-448.
Pawar, A. P., Dubay, K. F., Zurdo, J., Chiti, F., Vendruscolo, M.& Dobson, C. M. Prediction of "aggregation-prone" and "aggregation-susceptible" regions in proteins associated with neurodegenerative diseases. J. Mol. Biol.2005,350,379-392.
Permyakov, E. A.& Berliner, L. J. α-Lactalbumin:structure and function. FEBS Lett. 2000,473,269-274.
Permyakov, S. E., Pershikova, I. V., Zhadan, A. P., Goers, J., Bakunts, A. G.,. Uversky, V. N, Berliner, L. J., Permyakov, E. A. Conversion of human a-lactalbumin to an apo-like state in the complexes with basic poly-amino acids:toward understanding of the molecular mechanism of antitumor action of HAMLET. J. Proteome Res.2005,4, 564-569.
Permyakov, E. A., Reyzer, I. L.& Berliner, L. J. Effects of Zn(II) on galactosyltransferase activity. J. Protein Chem.1993,12,633-638.
Permyakov, E. A., Yarmolenko, V. V., Kalinichenko, L. P., Morozova, L. A.& Burstein, E. A. Calcium binding to a-lactalbumin:structural rearrangement and association constant evaluation by means of intrinsic protein fluorescence changes. Biochem. Biophys. Res. Commun.1981,100,191-197.
Pettersson, J., Aits, S., Gustafsson, L., Mossberg, A., Storm, P., Trulsson, M., Persson, F., Mok, K. H.& Svanborg, C. Can misfolded proteins be beneficial? The HAMLET case. Ann. Med.2009,41,162-176.
Pettersson, J., Mossberg, A. K.& Svanborg, C. a-Lactalbumin species variation, HAMLET formation, and tumor cell death. Biochem. Biophys. Res. Commun.2006,-345,260-270.
Plakoutsi, G., Bemporad, F., Calamai, M., Taddei, N., Dobson, C. M.& Chiti, F. Evidence for a mechanism of amyloid formation involving molecular reorganisation within native-like precursor aggregates. J. Mol. Biol.2005,351,910-922.
Polverino de Laureto, P., Frare, E., Gottardo, R., Van Dael, H.& Fontana, A. Partly folded states of members of the lysozyme/lactalbumin superfamily:a comparative study by circular dichroism spectroscopy and limited proteolysis. Protein Sci.2002, 11,2932-2946.
Polverino de Laureto, P., Taddei, N., Frare, E., Capanni, C., Costantini, S., Zurdo, J., Chiti, F., Dobson, C. M.& Fontana, A. Protein aggregation and amyloid fibril formation by an SH3 domain probed by limited proteolysis. J. Mol. Biol.2003,334, 129-141.
Pramanik, B. N., Bartner, P. L., Mirza, U. A., Liu, Y. H.& Ganguly, A. K. Electrospray ionization mass spectrometry for the study of non-covalent complexes: an emerging technology. J. Mass Spectrom.1998,33,911-920.
Prusiner, S. B. Prions. Proc. Natl. Acad. Sci. U. S. A.1998,95,13363-13383.
Ptitsyn, O. B. Protein folding:Hypotheses and experiments. Protein J.1987,6, 273-293.
Ptitsyn, O. B., Pain, R. H., Semisotnov, G. V., Zerovnik, E.& Razgulyaev, O. I. Evidence for a molten globule state as a general intermediate in protein folding. FEBS Lett.1990,262,20-24.
Ramstrom, H., Sanglier, S., Leize-Wagner, E., Philippe, C, Van Dorsselaer, A.& Haiech, J. Properties and regulation of the bifunctional enzyme HPr kinase/phosphatase in Bacillus subtilis. J. Biol. Chem:2003,278,1174-1185.
Ravikumar, B., Sarkar, S., Berger, Z.& et al. The roles of the ubiquitin-proteasome and autophagy-lysosome pathways in Huntington's disease and related conditions. Clin. Neurosci. Res.2003,3,141-148.
Reed, J. C. Dysregulation of apoptosis in cancer. J. Clin. Oncol.1999,17,2941-2953.
Redfield, C., Schulman, B. A., Milhollen, M. A., Kim, P. S.& Dobson, C. M. α-lactalbumin forms a compact molten globule in the absence of disulfide bonds. Nat. Struct. Biol.1999,6,948-952.
Riccardi, C., Nicoletti, I., Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat. Protoc.2006,1,1458-1461.
Rinia H.A., Snel M.M., van der Eerden J.P., de Kruijff B. Visualizing detergent resistant domains in model membranes with atomic force microscopy. FEBS Lett. 2001,501,92-96
Ross, C. A.& Poirier, M. A. What is the role of protein aggregation in neurodegeneration? Nat. Rev. Mol. Cell Biol.2005,6,891-898.
Safar, J., Roller, P. P., Gajdusek, D. C.& Gibbs, C. J., Jr. Conformational transitions, dissociation, and unfolding of scrapie amyloid (prion) protein. J. Biol. Chem.1993, 268,20276-20284.
Safar, J., Roller, P. P., Gajdusek, D. C.& Gibbs, C. J., Jr. Scrapie amyloid (prion) protein has the conformational characteristics of an aggregated molten globule folding intermediate. Biochemistry 1994,33,8375-8383.
Sasahara, K., Demura, M.& Nitta, K. Equilibrium and kinetic folding of hen egg-white lysozyme under acidic conditions. Proteins Struct. Funct. Genet.2002,49, 472-482.
Semisotnov, G. V., Rodionova, N. A., Kutyshenko, V. P.& Ptitsyn, O. B. Sequential mechanism of refolding of carbonic anhydrase B. FEBS Lett.1987,224,9-13.
Sharon, R., Bar-Joseph, I., Frosch, M. P., Walsh, D. M., Hamilton, J. A.& Selkoe, D. J. The formation of highly soluble oligomers of a-synuclein is regulated by fatty acids and enhanced in Parkinson's disease. Neuron 2003,37,583-595.
Smith, R. D., Loo, J. A., Edmonds, C. G, Barinaga, C. J.& Udseth, H. R. New Developments in Biochemical Mass Spectrometry:Electrospray Ionization. Anal. Chem.1990,62,882-899.
Sogbein, O. O., Simmons, D. A.& Konermann, L. Effects of pH on the kinetic reaction mechanism of myoglobin unfolding studied by time-resolved electrospray ionization mass spectrometry. J. Am. Soc. Mass Spectrom.2000,11,312-319.
Sommers, P. B.,& Kronman, M. J. Comparative fluorescence properties of bovine, goat, human and guinea pig a-lactalbumin. Characterization of the environments of individual tryptophan residues in partially folded conformers. Biophys. Chem.1980, 11,217-232.
Stefani, M. Protein misfolding and aggregation:new examples in medicine and biology of the dark side of the protein world. Biochim. Biophys. Acta 2004,1739, 5-25.
Stefani, M.& Dobson, C. M. Protein aggregation and aggregate toxicity:new insights into protein folding, misfolding diseases and biological evolution. J. Mol. Med.2003, 81,678-699.
Stites, W. E. Proteinminus signProtein Interactions:Interface Structure, Binding Thermodynamics, and Mutational Analysis. Chem. Rev.1997,97,1233-1250.
Stolz M., Stoffler D., Aebi U., et al. Monitoring biomolecular interactions by time-lapse atomic force microscopy. J. Struct. Biol.2000,131,171-180.
Sunde, M.& Blake, C. The structure of amyloid fibrils by electron microscopy and X-ray diffraction. Adv. Protein Chem.1997,50,123-159.
Svanborg, C., Agerstam, H., Aronson, A., Bjerkvig, R., Duringer, C., Fischer, W., Gustafsson, L., Hallgren, O., Leijonhuvud, I., Linse, S., Mossberg, A. K., Nilsson, H., Pettersson, J.& Svensson, M. HAMLET kills tumor cells by an apoptosis-like mechanism:cellular, molecular, and therapeutic aspects. Adv. Cancer. Res.2003,88, 1-29.
Svensson, M., Fast, J., Mossberg, A. K., Duringer, C., Gustafsson, L., Hallgren, O., Brooks, C. L., Berliner, L., Linse, S.& Svanborg, C. α-Lactalbumin unfolding is not sufficient to cause apoptosis, but is required for the conversion to HAMLET (human α-lactalbumin made lethal to tumor cells). Protein Sci.2003a,12,2794-2804.
Svensson, M., Hakansson, A., Mossberg, A. K., Linse, S.& Svanborg, C. Conversion of α-lactalbumin to a protein inducing apoptosis. Proc. Natl. Acad. Sci. U. S. A.2000, 97,4221-4226.
Svensson, M., Mossberg, A. K., Pettersson, J., Linse, S.& Svanborg, C. Lipids as cofactors in protein folding:stereo-specific lipid-protein interactions are required to form HAMLET (human α-lactalbumin made lethal to tumor cells). Protein Sci.2003b, 12,2805-2814.
Svensson, M., Sabharwal, H., Hakansson, A., Mossberg, A. K., Lipniunas, P., Leffler, H., Svanborg, C.& Linse, S. Molecular characterization of α-lactalbumin folding variants that induce apoptosis in tumor cells. J. Biol. Chem.1999,274,6388-6396.
Taylor, R. C., Cullen, S. P., Martin, S. J. Apoptosis:controlled demolition at the cellular level. Nat. Rev. Mol. Cell Biol.2008,9,231-241.
Todd, M. J.& Gomez, J. Enzyme kinetics determined using calorimetry:a general assay for enzyme activity? Anal. Biochem.2001,296,179-187.
Tompa, P., Szasz, C.& L. Buday. Structural disorder throws new light on moonlighting. Trends Biochem Sci.,2005,30,484-489.
Tsujimoto Y., Finger L.R., Yunis J., Nowell P.C.& Croce C.M. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14:18) chromsome translocation. Science.1984,226,1097-1099.
.Uversky, V. N., Garriques, L. N., Millett, I. S., Frokjaer, S., Brange, J., Doniach, S.& Fink, A. L. Prediction of the association state of insulin using spectral parameters. J. Pharm. Sci.2003,92,847-858.
Vander Heiden, M. G, Chandel, N. S., Williamson, E. K., Schumacker, P. T.& Thompson, C. B. Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria. Cell 1997,91,627-637.
Vermes, I., Haanen, C., Steffens-Nakken, H., Reutelingsperger, C. A novel assay for apoptosis:flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled annexin V. J. Immunol. Methods.1995,184, 39-51.
Ventura, S., Zurdo, J., Narayanan, S., Parreno, M., Mangues, R., Reif, B., Chiti, F., Giannoni, E., Dobson, C. M., Aviles, F. X.& Serrano, L. Short amino acid stretches can mediate amyloid formation in globular proteins:the Src homology 3 (SH3) case. Proc.Natl.Acad. Sci. U. S. A.2004,101,7258-7263.
Wain, R., Smith, L. J.& Dobson, C. M.. Oxidative refolding of amyloidogenic variants of human lysozyme. J. Mol. Biol.2005,351,662-671.
Wehbi, Z., Perez, M. D., Sanchez, L., Pocovi, C., Barbana, C.& Calvo, M. Effect of heat treatment on denaturation of bovine α-lactalbumin:determination of kinetic and thermodynamic parameters. J. Agric. Food Chem.2005,53,9730-9736.
Welch, K.& Yuan, J. α-synuclein oligomerization:a role for lipids? Trends Neurosci. 2003,26,517-519.
Wickner, S., Maurizi, M. R.& Gottesman, S. Posttranslational quality control:folding, refolding, and degrading proteins. Science 1999,286,1888-1893.
Wright, C. F., Teichmann, S. A., Clarke, J.& Dobson, C. M. The importance of sequence diversity in the aggregation and evolution of proteins. Nature 2005,438, 878-881.
Wyllie, A. H.V Kerr, J. F. R.& Currie, A. R. Cell Death:The significance of apotosis. Int Rev Cytol.1980,68,251-306.
Yang, F., Jr., Zhang, M., Chen, J.& Liang, Y. Structural changes of α-lactalbumin induced by low pH and oleic acid. Biochim. Biophys. Acta 2006a,1764,1389-1396.
Yang, F., Jr., Zhang, M., Zhou, B. R., Chen, J.& Liang, Y. Oleic acid inhibits amyloid formation of the intermediate of a-lactalbumin at moderately acidic pH. J. Mol. Biol.2006b,362,821-834.
Yang, F., Zhou, B. R., Zhang, P., Zhao, Y. F., Chen, J., Liang, Y. Binding of ferulic acid to cytochrome c enhances stability of the protein at physiological pH and inhibits cytochrome c-induced apoptosis. Chem.-Biol. Interact.2007,170,231-243.
Ye, X., Franco, A. A., Santos, H., Nelson, D. M., Kaufman, P. D.& Adams, P. D. Defective S phase chromatin assembly causes DNA damage, activation of the S phase checkpoint, and S phase arrest. Mol. Cell 2003,11,341-351.
Zhao, H., Tuominen, E. K.& Kinnunen, P. K. Formation of amyloid fibers triggered by phosphatidylserine-containing membranes. Biochemistry 2004,43,10302-10307.
Zweig, G.& Block, R. J. Studies on bovine whey proteins. Ⅲ. The preparation of crystalline a-lactalbumin and β-lactoglobulin ferrilactin. Arch. Biochem. Biophys. 1954,51,200-207.
梁毅结构生物学.(2005)科学出版社第一版193-236.
斯佩克特,戈德曼,莱因万德,黄培堂细胞实验指南.(2001)科学出版社.
王志珍蛋白质折叠和分子伴侣.生物学通报2004,39(5),1-6.
赵南明,周海梦生物物理学.(2004)高等教育出版社.
邹承鲁第二遗传密码.科学通报2000,45,1681-1687.
邹承鲁结构生物学的时代已经开始.科技导报1995,04(7),7-11.
Acharya, K. R., Ren, J. S., Stuart, D. I., Phillips, D. C.& Fenna, R. E. Crystal structure of human a-lactalbumin at 1.7 A resolution. J. Mol. Biol.1991,221, 571-581.
Acharya, K. R., Stuart, D. I., Phillips, D. C., McKenzie, H. A.& Teahan, C. G. Models of the three-dimensional structures of echidna, horse, and pigeon lysozymes: calcium-binding lysozymes and their relationship with a-lactalbumins. J. Protein Chem.1994,13,569-584.
Aits, S., Gustafsson, L., Hallgren,O., Brest, P., Gustafsson, M., Trulsson, M., Mossberg, A.K., Simon, H.U., Mograbi, B., Svanborg, C. HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death. Int J. Cancer.124,1008-1019.
Anfinsen, C. B., Haber, E., Sela, M.& White, Jr. F. H. The kinetics of formation of native ribonuclease during oxidation of the reduced polypeptide chain. Proc. Natl. Acad. Sci. U. S. A.1961,47,1309-1314.
Aramini, J. M., Hiraoki, T., Grace, M. R., Swaddle, T. W., Chiancone, E.& Vogel, H. J. NMR and stopped-flow studies of metal ion binding to a-lactalbumins. Biochim. Biophys. Acta 1996,1293,72-82.
Barbana, C., Perez, M. D., Sanchez, L., Dalgalarrondo, M., Chobert, J. M., Haertle, T. & Calvo, M. Interaction of bovine a-lactalbumin with fatty acids as determined by partition equilibrium and fluorescence spectroscopy. Int. Dairy J.2006,16,18-25.
Bates, S.& Vousden, K. H. Mechanisms of p53-mediated apoptosis. Cell Mol. Life Sci.1999,55,28-37.
Bhattacharjee, R. N., Park, K. S., Kumagai, Y., Okada, K., Yamamoto, M., Uematsu, S., Matsui, K., Kumar, H., Kawai, T., Iida, T.,Akira, S. VP1686, a Vibrio type Ⅲ secretion protein, induces toll-like receptor-independent apoptosis in macrophage through NF-κB Inhibition. J. Biol. Chem.2006,281,36897-36904.
Bomhoff, G., Sloan, K., McLain, C., Gogol, E. P.& Fisher, M. T. The effects of the flavonoid baicalein and osmolytes on the Mg2+ accelerated aggregation/fibrillation of carboxymethylated bovine 1SS-α-lactalbumin. Arch. Biochem. Biophys.2006,453, 75-86.
Booth, D. R., Sunde, M., Bellotti, V., Robinson, C. V., Hutchinson, W. L., Fraser, P. E., Hawkins, P. N., Dobson, C. M., Radford, S. E., Blake, C. C.& Pepys, M. B. Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis. Nature 1997,385,787-793.
Bucciantini, M., Calloni, G., Chiti, F., Formigli, L., Nosi, D., Dobson, C. M.& Stefani, M.. Prefibrillar amyloid protein aggregates share common features of cytotoxicity. J. Biol. Chem.2004,279,31374-31382.
Bucciantini, M., Giannoni, E., Chiti, F., Baroni, F., Formigli, L., Zurdo, J., Taddei, N., Ramponi,G., Dobson, C. M.& Stefani, M. Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 2002,416,507-511.
Bushmarina, N. A., Kuznetsova, I. M., Biktashev, A. G., Turoverov, K. K., Uversky, V. N. Partially folded conformations in the folding pathway of bovine carbonic anhydrase Ⅱ:a fluorescence spectroscopic analysis. Chembiochem 2001,2(11): 813-821.
Calamai, M., Canale, C., Relini, A., Stefani, M., Chiti, F.& Dobson, C. M. Reversal of protein aggregation provides evidence for multiple aggregated States. J. Mol. Biol. 2005,346,603-616.
Calamai, M., Chiti, F.& Dobson, C. M. Amyloid fibril formation can proceed from different conformations of a partially unfolded protein. Biophys. J.2005,89, 4201-4210.
Carulla, N., Caddy, G L., Hall, D. R., Zurdo, J., Gairi, M., Feliz, M., Giralt, E., Robinson, C. V.& Dobson, C. M. Molecular recycling within amyloid fibrils. Nature 2005,436,554-558.
Cawthern, K. M., Permyakov, E., Berliner, L. J. Membrane-bound states of α-lactalbumin:implications for the protein stability and conformation. Protein Sci.1996,5,1394-1405.
Cawthern, K. M., Narayan, M., Chaudhuri, D., Permyakov, E. A., Berliner, L. J., Interactions of a-lactalbumin with fatty acids and spin label analogs. J. Biol. Chem. 1997,272,30812-30816.
Chandra, N., Brew, K.& Acharya, K. R. Structural evidence for the presence of a secondary calcium binding site in human a-lactalbumin. Biochemistry 1998,37, 4767-4772.
Chiti, F., Bucciantini, M., Capanni, C, Taddei, N., Dobson, C. M.& Stefani, M. Solution conditions can promote formation of either amyloid protofilaments or mature fibrils from the HypF N-terminal domain. Protein Sci.2001,10,2541-2547.
Chiti, F., De Lorenzi, E., Grossi, S., Mangione, P., Giorgetti, S., Caccialanza, G., Dobson, C. M., Merlini, G., Ramponi, G.& Bellotti, V. A partially structured species of beta 2-microglobulin is significantly populated under physiological conditions and involved in fibrillogenesis. J. Biol. Chem.2001,276,46714-21.
Chiti, F.& Dobson, C. M. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem.2006,75,333-366.
Chiti, F., Mangione, P., Andreola, A., Giorgetti, S., Stefani, M., Dobson, C. M., Bellotti, V.& Taddei, N. Detection of two partially structured species in the folding process of the amyloidogenic protein beta 2-microglobulin. J. Mol. Biol.2001,307, 379-391.
Chiti, F., Stefani, M., Taddei, N., Ramponi, G.& Dobson, C. M. Rationalization of the effects of mutations on peptide and protein aggregation rates. Nature 2003,424, 805-808.
Chiti, F., Taddei, N., Bucciantini, M., White, P., Ramponi, G.& Dobson, C. M. Mutational analysis of the propensity for amyloid formation by a globular protein. Embo J.2000,19,1441-1449.
Cistola, D. P., Hamilton, J. A., Jackson, D.& Small, D. M. Ionization and phase behavior of fatty acids in water:application of the Gibbs phase rule. Biochemistry 1988,27,1881-1888.
Darzynkiewicz, Z., Gong, J. P., Traganos, F. Expression of cell-cycle specific proteins cyclins as a marker of the cell-cycle position, independent of DNA content, in:Z. Darzynkiewicz, P. J. Robinson, H. A. Crissman (Eds.), Flow Cytometry,2nd Edition, Academic Press, San Diego, CA,1994.
De Felice, F. G., Vieira, M. N., Meirelles, M. N., Morozova-Roche, L. A., Dobson, C. M.& Ferreira, S. T. Formation of amyloid aggregates from human lysozyme and its disease-associated variants using hydrostatic pressure. Faseb J.2004,18,1099-1101. de Laureto, P. P., Frare, E., Gottardo, R., Van Dael, H.& Fontana, A. Partly folded states of members of the lysozyme/lactalbumin superfamily:a comparative study by circular dichroism spectroscopy and limited proteolysis. Protein Sci.2002,11, 2932-2946.
de Laureto, P. P., Frare, E., Battaglia, F., Mossuto, M. F., Uversky, V. N.& Fontana, A. Protein dissection enhances the amyloidogenic properties of α-lactalbumin. FEBS J.2005,272,2176-2188.
Dirix, C., Meersman, F., MacPhee, C. E., Dobson, C. M.& Heremans, K. High hydrostatic pressure dissociates early aggregates of TTR105-115, but not the mature amyloid fibrils. J. Mol. Biol.2005,347,903-909.
Dobson, C. M. Experimental investigation of protein folding and misfolding. Methods 2004,34,4-14.
Dobson, C. M. Protein chemistry. In the footsteps of alchemists. Science 2004,304, 1259-62.
Dobson, C. M. Protein misfolding, evolution and disease. Trends Biochem. Sci.1999, 24,329-332.
Dobson, C. M. Principles of protein folding, misfolding and aggregation. Semin. Cell Dev. Biol.2004,15,3-16.
Dobson, C. M. Structural biology:prying into prions. Nature 2005,435,747-749.
Dobson, C. M.& Ellis, R. J. Protein folding and misfolding inside and outside the cell. Embo J.1998,17,5251-5254.
Dolgikh, D. A., Abaturov, L. V., Bolotinna, I. A., Brazhnikov, E. V., Bychkova, V. E., .Gilmanshin, R. I., Lebedev, Yu.O., Semisotnov, G. V., Tiktopulo, E. I.& Ptitsyn, O. B. Compact state of a protein molecule with pronounced small-scale mobility:bovine a-lactalbumin. Eur. Biophys. J.1985,13,109-120.
Dolgikh, D. A., Gilmanshin, R. I., Brazhnikov, E. V., Bychkova, V. E., Semisotnov, G. V., Venyaminov, S.& Ptitsyn, O. B. α-Lactalbumin:compact state with fluctuating tertiary structure? FEBS Lett.1981,136,311-315.
DuBay, K. F., Pawar, A. P., Chiti, F., Zurdo, J., Dobson, C. M.& Vendruscolo, M. Prediction of the absolute aggregation rates of amyloidogenic polypeptide chains. J. Mol. Biol.2004,341,1317-1326.
van, Duijn, E., Bakkes, P. J., Heeren, R. M., van, den, Heuvel, R. H., van, Heerikhuizen, H., van, der, Vies, S. M.,. Heck, A.J. Monitoring macromolecular complexes-involved in the chaperonin-assisted protein folding cycle by mass spectrometry.Nat.Methods.2005,2,371-376.
Dumoulin, M., Canet, D., Last, A. M., Pardon, E., Archer, D. B., Muyldermans, S., Wyns, L., Matagne, A., Robinson, C. V., Redfield, C.& Dobson, C. M. Reduced global cooperativity is a common feature underlying the amyloidogenicity of pathogenic lysozyme mutations. J. Mol. Biol.2005,346,773-788.
Duringer, C., Hamiche, A., Gustafsson, L., Kimura, H.& Svanborg, C. HAMLET interacts with histones and chromatin in tumor cell nuclei. J. Biol. Chem.2003,278, 42131-42135.
Eftink, M. R.& Ghiron, C. A. Fluorescence quenching studies with proteins. Anal. Biochem.1981,114,199-227.
Ellis, R. J.& Hartl, F. U. Principles of protein folding in the cellular environment. Gurr.Opin. Struct. Biol.1999,9,102-110.
Engebraaten, O., Hjortland, G. O., Hirschberg, H.& Fodstad, O. Growth of precultured human glioma specimens in nude rat brain. J. Neurosurg.1999,90, 125-132.
Fandrich, M., Fletcher, M. A.& Dobson, C.M. Amyloid fibrils from muscle myoglobin. Nature 2001,410,165-166.
Fandrich, M.& Dobson, C. M. The behaviour of polyamino acids reveals an inverse side chain effect in amyloid structure formation. Embo J.2002,21,5682-5690.
Fast, J., Mossberg, A. K., Nilsson, H., Svanborg, C., Akke, M.& Linse, S. Compact oleic acid in HAMLET. FEBS Lett.2005,579,6095-6100.
Fischer, W., Gustafsson, L., Mossberg, A. K., Gronli, J., Mork, S., Bjerkvig, R.& Svanborg, C. Human a-lactalbumin made lethal to tumor cells (HAMLET) kills human glioblastoma cells in brain xenografts by an apoptosis-like mechanism and prolongs survival. Cancer Res.2004,64,2105-2112.
Frare, E., Polverino De Laureto, P., Zurdo, J., Dobson, C. M.& Fontana, A. A highly amyloidogenic region of hen lysozyme. J.Mol. Biol.2004,340,1153-1165.
Gharibyan, A. L., Zamotin, V., Yanamandra, K., Moskaleva, O. S., Margulis, B. A., Kostanyan, I. A., Morozova-Roche, L. A. Lysozyme amyloid oligomers and fibrils induce cellular death via different apoptotic/necrotic pathways. J. Mol. Biol.2007,365, 1337-1349.
Goldsbury, C., Kistler, J., Aebi, U., Arvinte, T.& Cooper, G J.. Watching amyloid fibrils grow by time-lapse atomic force microscopy. J. Mol. Biol.1999,285,33-39.
Gosal, W. S., Clark, A. H.& Ross-Murphy, S. B. Fibrillar beta-lactoglobulin gels:Part 1. Fibril formation and structure. Biomacromolecules 2004,5,2408-2419.
Green, D. R.& Kroemer, G The pathophysiology of mitochondrial cell death. Science 2004,50,626-629.
Gundersen, S., Lote, K.& Hannisdal, E. Prognostic factors for glioblastoma multiforme-development of a prognostic index. Acta Oncol.1996,35 (Suppl.8), 123-127.
Gussakovsky, E. E., Haas, E. Two steps in the transition between the native and acid states of bovine a-lactalbumin detected by circular polarization of luminescence: evidence for a premolten globule state? Protein Sci.1995,4,2319-2326.
Gustafsson, L., Hallgren, O., Mossberg, A. K., Pettersson, J., Fischer, W., Aronsson, A. & Svanborg, C. HAMLET kills tumor cells by apoptosis:structure, cellular mechanisms, and therapy. J. Nutr.2005,135,1299-1303.
Gustafsson, L., Leijonhufvud, I., Aronsson, A., Mossberg, A. K.& Svanborg, C. Treatment of skin papillomas with topical a-lactalbumin-oleic acid. N. Engl. J. Med. 2004,350,2663-2672.
Goers, J., Permyakov, S. E., Permyakov, E. A., Uversky, V. N.& Fink, A. L. Conformational prerequisites for a-lactalbumin fibrillation. Biochemistry 2002,41, 12546-12551.
Hakansson, A., Andreasson, J., Zhivotovsky, B., Karpman, D., Orrenius, S.& Svanborg, C. Multimeric α-lactalbumin from human milk induces apoptosis through a direct effect on cell nuclei. Exp. Cell Res.1999,246,451-460.
Hakansson, A., Zhivotovsky, B., Orrenius, S., Sabharwal, H.& Svanborg, C. Apoptosis induced by a human milk protein. Proc. Natl. Acad. Sci. U. S. A.1995,92, 8064-8068.
Hall, D., Hirota, N.& Dobson, C. M. A toy model for predicting the rate of amyloid formation from unfolded protein. J. Mol Biol.2005,351,195-205.
Hallgren, O., Gustafsson, L., Irjala, H., Selivanova, G., Orrenius, S.& Svanborg, C. HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53.Apoptosis 2006,11,221-233.
Halliburton, W.D. The Proteids of Milk. J. Physiol. 1890,11,448-463.
Hamada, D.& Dobson, C.M. A kinetic study of beta-lactoglobulin amyloid fibril formation promoted by urea. Protein Sci.2002,11,2417-2426.
Hamodrakas, S. J., Hoenger, A.& Iconomidou, V. A. Amyloid fibrillogenesis of silkmoth chorion protein peptide-analogues via a liquid-crystalline intermediate phase. J. Struct. Biol.2004,145,226-235.
Harper, J. D.& Lansbury, P. T., Jr. Models of amyloid seeding in Alzheimer's disease and scrapie:mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteins. Annu. Rev. Biochem.1997,66,385-407.
Hartl, F. U. Molecular chaperones in cellular protein folding. Nature 1996,381, 571-580.
Ikeguchi, M., Kuwajima, K., Mitani, M.& Sugai, S. Evidence for identity between the equilibrium unfolding intermediate and a transient folding intermediate:a .comparative study of the folding reactions of α-lactalbumin and lysozyme. Biochemistry 1986,25,6965-6972.
Jaroniec, C. P., MacPhee, C. E., Astrof, N. S., Dobson, C. M.& Griffin, R. G. Molecular conformation of a peptide fragment of transthyretin in an amyloid fibril. Proc. Natl.Acad. Sci. U. S. A.2002,99,16748-16753.
Jaroniec, C. P., MacPhee, C. E., Bajaj, V. S., McMahon, M. T., Dobson, C. M.& Griffin, R. G. High-resolution molecular structure of a peptide in an amyloid fibril determined by magic angle spinning NMR spectroscopy. Proc. Natl.Acad. Sci. U. S. A.2004,101,711-716.
Jeffery, C.J., Moonlighting proteins. Trends Biochem Sci,1994,24,8-11.
Jeffery, C.J., Moonlighting proteins:old proteins learning new tricks. Trends Genet, 2003,19,415-417.
Jimenez, J. L., Nettleton, E. J., Bouchard, M., Robinson, C. V., Dobson, C. M.& Saibil, H. R. The protofilament structure of insulin amyloid fibrils. Proc. Natl.Acad. Sci. U. S. A.2002,99,9196-9201.
Johnson, R. J., Christodoulou, J., Dumoulin, M., Caddy, G. L., Alcocer, M. J., Murtagh, G. J., Kumita, J. R., Larsson, G., Robinson, C. V., Archer, D. B., Luisi, B. & Dobson, C. M. Rationalising lysozyme amyloidosis:insights from the structure and solution dynamics of T70N lysozyme.J. Mol. Biol.2005,352,823-836.
Kammerer, R. A., Kostrewa, D., Zurdo, J., Detken, A., Garcia-Echeverria, C., Green, J. D., Muller, S. A., Meier, B. H., Winkler, F. K., Dobson, C. M.& Steinmetz, M. O. Exploring amyloid formation by a de novo design. Proc. Natl.Acad. Sci. U. S. A. 2004,101,4435-4440.
Katsarou, M. E., Efthimiadou, E. K, Psomas, G, Karaliota, A., Vourloumis, D. Novel copper(Ⅱ) complex of N-propyl-norfloxacin and 1,10-phenanthroline with enhanced antileukemic and DNA nuclease activities. J. Med. Chem.2008,51,470-478.
Kelly, J. W. The environmental dependency of protein folding best explains prion and amyloid diseases. Proc. Natl. Acad Sci. U. S. A.1998,95,930-932.
Kim, Y. J., Nakatomi, R., Akagi, T., Hashikawa, T.& Takahashi, R. Unsaturated fatty acids induce cytotoxic aggregate formation of amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutants. J. Biol. Chem.2005,280,21515-21521.
Kohler, C., Gogvadze, V., Hakansson, A., Svanborg, C., Orrenius, S.& Zhivotovsky, B. A folding variant of human a-lactalbumin induces mitochondrial permeability transition in isolated mitochondria. Eur. J. Biochem.2001,268,186-191.
Kohler, C., Hakansson, A., Svanborg, C., Orrenius, S.& Zhivotovsky, B. Protease activation in apoptosis induced by MAL. Exp. Cell Res.1999,249,260-268.
Konermann, L.& Douglas, D. J. Acid-induced unfolding of cytochrome c at different methanol concentrations:electrospray ionization mass spectrometry specifically monitors changes in the tertiary structure. Biochemistry 1997,36,12296-12302.
Konermann, L.& Douglas, D. J. Equilibrium unfolding of proteins monitored by electrospray ionization mass spectrometry:distinguishing two-state from multi-state transitions. Rapid Commun. Mass Spectrom.1998,12,435-442.
Kostovay Z.& Wolf, D. H. For whom the bell tolls:protein quality control of the endoplasmic reticulum and the ubiquitin-proteasome connection. EMBO. J.2003,22, 2309-2317.
Krebs, M. R., Macphee, C. E., Miller, A. F., Dunlop, I. E., Dobson, C. M.& Donald, A. M. The formation of spherulites by amyloid fibrils of bovine insulin. Proc. Natl. Acad. Sci. U. S. A.2004,101,14420-14424.
Krebs, M. R., Morozova-Roche, L. A., Daniel, K., Robinson, C. V.& Dobson, C. M. Observation of sequence specificity in the seeding of protein amyloid fibrils. Protein Sci.2004,13,1933-1938.
Krebs, M. R., Wilkins, D. K., Chung, E. W., Pitkeathly, M. C., Chamberlain, A. K., Zurdo, J., Robinson, C. V.& Dobson, C. M. Formation and seeding of amyloid fibrils from wild-type hen lysozyme and a peptide fragment from the beta-domain. J. Mol. Biol. 2000,300,541-549.
Kronman, M. J., Andreotti, R.& Vitols, R. Inter- and intramolecular interactions of a-Lactalbumin. Ⅱ. Aggregation reactions at acid pH. Biochemistry 1964,3, 1152-1160.
Kuwajima, K. A folding model of a-lactalbumin deduced from the three-state denaturation mechanism. J. Mol. Biol.1977,114,241-258.
Kuwajima, K., Mitani, M.& Sugai, S. Characterization of the critical state in protein folding. Effects of guanidine hydrochloride and specific Ca2+ binding on the folding kinetics of α-lactalbumin. J. Mol. Biol.1989,206,547-561.
Kuwajima, K. The molten globule state of α-lactalbumin. Faseb. J.1996,10, 102-109.
Kuznetsova, I. M., Stepanenko, O. V., Turoverov, K. K., Zhu, L., Fan, Y. X., Zhou, J. M., Fink, A. L.& Uversky, V. N. Unraveling multistate unfolding of rabbit muscle creatine kinase. Biochim. Biophys. Acta 2002,1596,138-155.
Lala, A. K., Kaul, P. Increased exposure of hydrophobic surface in molten globule state of α-lactalbumin. Fluorescence and hydrophobic photolabeling studies. J. Biol. Chem.1992,267,19914-19918.
Lane, D. P. Cancer. A death in the life of p53. Nature 1993,362,786-787.
Lansbury, P. T., Jr. Evolution of amyloid:what normal protein folding may tell us about fibrillogenesis and disease. Proc. Natl. Acad. Sci. U. S. A.1999,96,3342-3344.
Lehrer, S. S. Solute perturbation of protein fluorescence. The quenching of the tryptophyl fluorescence of model compounds and of lysozyme by iodide ion. Biochemistry 1971,10,3254-3263.
Liang, Y., Du, F., Sanglier, S., Zhou, B. R., Xia, Y, Dorsselaer, A. V., Maechling, C., Kilhoffer, M. C.& Haiech, J. Unfolding of Rabbit Muscle Creatine Kinase Induced by Acid:A study using electrospray ionization mass spectrometry, isothermal titration calorimetry, and fluorescence spectroscopy. J. Biol. Chem.2003,278,30098-30105.
Liang, Y. Applications of isothermal titration calorimetry in protein science. Acta Biochim. Biophys. Sin.2008,40,565-576.
Liang, Y, Huang, G. C., Chen, J.& Zhou, J. M. Microcalorimetric studies on the unfolding of creatine kinase induced by guanidine hydrochloride. Thermochim. Acta 2001,376,123-131.
Lonnerdal, B.& Lien, E. L. Nutritional and physiologic significance of a-lactalbumin in infants. Nutr. Rev.2003,61,295-305.
Lopez De La Paz, M., Goldie, K., Zurdo, J., Lacroix, E., Dobson, C. M., Hoenger, A. & Serrano, L. De novo designed peptide-based amyloid fibrils. Proc. Natl. Acad. Sci. U. S.A:2002,99,16052-16057.
Ma, Z.& Westermark, G. T. Effects of free fatty acid on polymerization of islet amyloid polypeptide (IAPP) in vitro and on amyloid fibril formation in cultivated isolated islets of transgenic mice overexpressing human IAPP. Mol Med.2002,8, 863-868.
MacPhee, C. E.& Dobson, C. M. Chemical dissection and reassembly of amyloid fibrils formed by a peptide fragment of transthyretin. J. Mol. Biol 2000,297, 1203-1215.
Malisauskas, M., Zamotin, V., Jass, J., Noppe, W., Dobson, C. M.& Morozova-Roche, L. A. Amyloid protofilaments from the calcium-binding protein equine lysozyme: formation of ring and linear structures depends on pH and metal ion concentration. J. Mol. Biol.2003,330,879-890.
Malisauskas, M., Ostman, J., Darinskas, A., Zamotin, V., Liutkevicius, E., Lundgren, E., Morozova-Roche, L. A. Does the cytotoxic effect of transient amyloid oligomers from common equine lysozyme in vitro imply innate amyloid toxicity? J. Biol. Chem. 2005,280,6269-6275.
Makhatadze, G. I.& Privalov, P. L. Protein interactions with urea and guanidinium chloride. A calorimetric study. J. Mol. Biol. 1992,226,491-505.
Makhatadze, G I. Thermodynamics of protein interactions with urea and guanidinium hydrochloride. J. Phys.Chem.1999,103,4781-4784.
Marcon, G., Plakoutsi, G., Canale, C., Relini, A., Taddei, N., Dobson, C. M., Ramponi, G & Chiti, F. Amyloid formation from HypF-N under conditions in which the protein is initially in its native state. J. Mol. Biol 2005,347,323-335.
Marek, P., Abedini, A., Song, B., Kanungo, M., Johnson, M. E., Gupta, R., Zaman, W., Wong, S. S.& Raleigh, D. P.. Aromatic Interactions Are Not Required for Amyloid Fibril Formation by Islet Amyloid Polypeptide but Do Influence the Rate of Fibril Formation and Fibril Morphology. Biochemistry 2007,46,3255-3261.
Mastrangelo, I. A., Ahmed, M., Sato, T., Liu, W., Wang, C., Hough, P.& Smith, S. O. High-resolution atomic force microscopy of soluble Abeta42 oligomers. J. Mol. Biol. 2006,358,106-119.
Mathur, G. P., Gupta, N., Mathur, S., Gupta, V., Pradhan, S., Dwivedi, J. N., Tripathi, B. N., Kushwaha, K. P., Sathy, N., Modi, U. J.& et al. Breastfeeding and childhood cancer. Indian Pediatr.1993,30,651-657.
McKenzie, H. A.& White, F. H., Jr., Studies on a trace cell lytic activity associated with α-lactalbumin. Biochem. Int.1987,14,347-356.
Meehan, S., Berry, Y., Luisi, B., Dobson, C. M., Carver, J. A.& MacPhee, C. E. Amyloid fibril formation by lens crystallin proteins and its implications for cataract formation. J. Biol. Chem.2004,279,3413-3419.
Mok, K. H., Pettersson, J., Orrenius, S.& Svanborg, C. HAMLET, protein folding, and tumor cell death. Biochem. Biophys. Res. Commun.2007,354,1-7.
Mosmann, T., Rapid colorimetric assay for cellular growth and survival:application to proliferation and cytotoxicity assays. J. Immunol. Methods.1983,65,55-63.
Munishkina, L. A., Fink, A. L.& Uversky, V. N. Conformational prerequisites for formation of amyloid fibrils from histones. J. Mol. Biol.2004,342,1305-1324.
Naiki, H., Higuchi, K., Hosokawa, M.& Takeda, T. Fluorometric determination of amyloid fibrils in vitro using the fluorescent dye, thioflavin T1. Anal. Biochem.1989, 177,244-249.
Nilsson, M. R.& Dobson, C. M. Chemical modification of insulin in amyloid fibrils. Protein Sci.2003,12,2637-2641.
Nilsson, M. R.& Dobson, C. M. In vitro characterization of lactoferrin aggregation and amyloid formation. Biochemistry 2003,42,375-382.
Ohgushi, M.& Wada, A.'Molten-globule state':a compact form of globular proteins with mobile side-chains. FEBS Lett.1983,14,21-24.
Pellegrini, A., Thomas, U., Bramaz, N., Hunziker, P.& von Fellenberg, R. Isolation and identification of three bactericidal domains in the bovine a-lactalbumin molecule. Biochim. Biophys. Acta 1999,1426,439-448.
Pawar, A. P., Dubay, K. F., Zurdo, J., Chiti, F., Vendruscolo, M.& Dobson, C. M. Prediction of "aggregation-prone" and "aggregation-susceptible" regions in proteins associated with neurodegenerative diseases. J. Mol. Biol.2005,350,379-392.
Permyakov, E. A.& Berliner, L. J. α-Lactalbumin:structure and function. FEBS Lett. 2000,473,269-274.
Permyakov, S. E., Pershikova, I. V., Zhadan, A. P., Goers, J., Bakunts, A. G.,. Uversky, V. N, Berliner, L. J., Permyakov, E. A. Conversion of human a-lactalbumin to an apo-like state in the complexes with basic poly-amino acids:toward understanding of the molecular mechanism of antitumor action of HAMLET. J. Proteome Res.2005,4, 564-569.
Permyakov, E. A., Reyzer, I. L.& Berliner, L. J. Effects of Zn(II) on galactosyltransferase activity. J. Protein Chem.1993,12,633-638.
Permyakov, E. A., Yarmolenko, V. V., Kalinichenko, L. P., Morozova, L. A.& Burstein, E. A. Calcium binding to a-lactalbumin:structural rearrangement and association constant evaluation by means of intrinsic protein fluorescence changes. Biochem. Biophys. Res. Commun.1981,100,191-197.
Pettersson, J., Aits, S., Gustafsson, L., Mossberg, A., Storm, P., Trulsson, M., Persson, F., Mok, K. H.& Svanborg, C. Can misfolded proteins be beneficial? The HAMLET case. Ann. Med.2009,41,162-176.
Pettersson, J., Mossberg, A. K.& Svanborg, C. a-Lactalbumin species variation, HAMLET formation, and tumor cell death. Biochem. Biophys. Res. Commun.2006,-345,260-270.
Plakoutsi, G., Bemporad, F., Calamai, M., Taddei, N., Dobson, C. M.& Chiti, F. Evidence for a mechanism of amyloid formation involving molecular reorganisation within native-like precursor aggregates. J. Mol. Biol.2005,351,910-922.
Polverino de Laureto, P., Frare, E., Gottardo, R., Van Dael, H.& Fontana, A. Partly folded states of members of the lysozyme/lactalbumin superfamily:a comparative study by circular dichroism spectroscopy and limited proteolysis. Protein Sci.2002, 11,2932-2946.
Polverino de Laureto, P., Taddei, N., Frare, E., Capanni, C., Costantini, S., Zurdo, J., Chiti, F., Dobson, C. M.& Fontana, A. Protein aggregation and amyloid fibril formation by an SH3 domain probed by limited proteolysis. J. Mol. Biol.2003,334, 129-141.
Pramanik, B. N., Bartner, P. L., Mirza, U. A., Liu, Y. H.& Ganguly, A. K. Electrospray ionization mass spectrometry for the study of non-covalent complexes: an emerging technology. J. Mass Spectrom.1998,33,911-920.
Prusiner, S. B. Prions. Proc. Natl. Acad. Sci. U. S. A.1998,95,13363-13383.
Ptitsyn, O. B. Protein folding:Hypotheses and experiments. Protein J.1987,6, 273-293.
Ptitsyn, O. B., Pain, R. H., Semisotnov, G. V., Zerovnik, E.& Razgulyaev, O. I. Evidence for a molten globule state as a general intermediate in protein folding. FEBS Lett.1990,262,20-24.
Ramstrom, H., Sanglier, S., Leize-Wagner, E., Philippe, C, Van Dorsselaer, A.& Haiech, J. Properties and regulation of the bifunctional enzyme HPr kinase/phosphatase in Bacillus subtilis. J. Biol. Chem:2003,278,1174-1185.
Ravikumar, B., Sarkar, S., Berger, Z.& et al. The roles of the ubiquitin-proteasome and autophagy-lysosome pathways in Huntington's disease and related conditions. Clin. Neurosci. Res.2003,3,141-148.
Reed, J. C. Dysregulation of apoptosis in cancer. J. Clin. Oncol.1999,17,2941-2953.
Redfield, C., Schulman, B. A., Milhollen, M. A., Kim, P. S.& Dobson, C. M. α-lactalbumin forms a compact molten globule in the absence of disulfide bonds. Nat. Struct. Biol.1999,6,948-952.
Riccardi, C., Nicoletti, I., Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat. Protoc.2006,1,1458-1461.
Rinia H.A., Snel M.M., van der Eerden J.P., de Kruijff B. Visualizing detergent resistant domains in model membranes with atomic force microscopy. FEBS Lett. 2001,501,92-96
Ross, C. A.& Poirier, M. A. What is the role of protein aggregation in neurodegeneration? Nat. Rev. Mol. Cell Biol.2005,6,891-898.
Safar, J., Roller, P. P., Gajdusek, D. C.& Gibbs, C. J., Jr. Conformational transitions, dissociation, and unfolding of scrapie amyloid (prion) protein. J. Biol. Chem.1993, 268,20276-20284.
Safar, J., Roller, P. P., Gajdusek, D. C.& Gibbs, C. J., Jr. Scrapie amyloid (prion) protein has the conformational characteristics of an aggregated molten globule folding intermediate. Biochemistry 1994,33,8375-8383.
Sasahara, K., Demura, M.& Nitta, K. Equilibrium and kinetic folding of hen egg-white lysozyme under acidic conditions. Proteins Struct. Funct. Genet.2002,49, 472-482.
Semisotnov, G. V., Rodionova, N. A., Kutyshenko, V. P.& Ptitsyn, O. B. Sequential mechanism of refolding of carbonic anhydrase B. FEBS Lett.1987,224,9-13.
Sharon, R., Bar-Joseph, I., Frosch, M. P., Walsh, D. M., Hamilton, J. A.& Selkoe, D. J. The formation of highly soluble oligomers of a-synuclein is regulated by fatty acids and enhanced in Parkinson's disease. Neuron 2003,37,583-595.
Smith, R. D., Loo, J. A., Edmonds, C. G, Barinaga, C. J.& Udseth, H. R. New Developments in Biochemical Mass Spectrometry:Electrospray Ionization. Anal. Chem.1990,62,882-899.
Sogbein, O. O., Simmons, D. A.& Konermann, L. Effects of pH on the kinetic reaction mechanism of myoglobin unfolding studied by time-resolved electrospray ionization mass spectrometry. J. Am. Soc. Mass Spectrom.2000,11,312-319.
Sommers, P. B.,& Kronman, M. J. Comparative fluorescence properties of bovine, goat, human and guinea pig a-lactalbumin. Characterization of the environments of individual tryptophan residues in partially folded conformers. Biophys. Chem.1980, 11,217-232.
Stefani, M. Protein misfolding and aggregation:new examples in medicine and biology of the dark side of the protein world. Biochim. Biophys. Acta 2004,1739, 5-25.
Stefani, M.& Dobson, C. M. Protein aggregation and aggregate toxicity:new insights into protein folding, misfolding diseases and biological evolution. J. Mol. Med.2003, 81,678-699.
Stites, W. E. Proteinminus signProtein Interactions:Interface Structure, Binding Thermodynamics, and Mutational Analysis. Chem. Rev.1997,97,1233-1250.
Stolz M., Stoffler D., Aebi U., et al. Monitoring biomolecular interactions by time-lapse atomic force microscopy. J. Struct. Biol.2000,131,171-180.
Sunde, M.& Blake, C. The structure of amyloid fibrils by electron microscopy and X-ray diffraction. Adv. Protein Chem.1997,50,123-159.
Svanborg, C., Agerstam, H., Aronson, A., Bjerkvig, R., Duringer, C., Fischer, W., Gustafsson, L., Hallgren, O., Leijonhuvud, I., Linse, S., Mossberg, A. K., Nilsson, H., Pettersson, J.& Svensson, M. HAMLET kills tumor cells by an apoptosis-like mechanism:cellular, molecular, and therapeutic aspects. Adv. Cancer. Res.2003,88, 1-29.
Svensson, M., Fast, J., Mossberg, A. K., Duringer, C., Gustafsson, L., Hallgren, O., Brooks, C. L., Berliner, L., Linse, S.& Svanborg, C. α-Lactalbumin unfolding is not sufficient to cause apoptosis, but is required for the conversion to HAMLET (human α-lactalbumin made lethal to tumor cells). Protein Sci.2003a,12,2794-2804.
Svensson, M., Hakansson, A., Mossberg, A. K., Linse, S.& Svanborg, C. Conversion of α-lactalbumin to a protein inducing apoptosis. Proc. Natl. Acad. Sci. U. S. A.2000, 97,4221-4226.
Svensson, M., Mossberg, A. K., Pettersson, J., Linse, S.& Svanborg, C. Lipids as cofactors in protein folding:stereo-specific lipid-protein interactions are required to form HAMLET (human α-lactalbumin made lethal to tumor cells). Protein Sci.2003b, 12,2805-2814.
Svensson, M., Sabharwal, H., Hakansson, A., Mossberg, A. K., Lipniunas, P., Leffler, H., Svanborg, C.& Linse, S. Molecular characterization of α-lactalbumin folding variants that induce apoptosis in tumor cells. J. Biol. Chem.1999,274,6388-6396.
Taylor, R. C., Cullen, S. P., Martin, S. J. Apoptosis:controlled demolition at the cellular level. Nat. Rev. Mol. Cell Biol.2008,9,231-241.
Todd, M. J.& Gomez, J. Enzyme kinetics determined using calorimetry:a general assay for enzyme activity? Anal. Biochem.2001,296,179-187.
Tompa, P., Szasz, C.& L. Buday. Structural disorder throws new light on moonlighting. Trends Biochem Sci.,2005,30,484-489.
Tsujimoto Y., Finger L.R., Yunis J., Nowell P.C.& Croce C.M. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14:18) chromsome translocation. Science.1984,226,1097-1099.
.Uversky, V. N., Garriques, L. N., Millett, I. S., Frokjaer, S., Brange, J., Doniach, S.& Fink, A. L. Prediction of the association state of insulin using spectral parameters. J. Pharm. Sci.2003,92,847-858.
Vander Heiden, M. G, Chandel, N. S., Williamson, E. K., Schumacker, P. T.& Thompson, C. B. Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria. Cell 1997,91,627-637.
Vermes, I., Haanen, C., Steffens-Nakken, H., Reutelingsperger, C. A novel assay for apoptosis:flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled annexin V. J. Immunol. Methods.1995,184, 39-51.
Ventura, S., Zurdo, J., Narayanan, S., Parreno, M., Mangues, R., Reif, B., Chiti, F., Giannoni, E., Dobson, C. M., Aviles, F. X.& Serrano, L. Short amino acid stretches can mediate amyloid formation in globular proteins:the Src homology 3 (SH3) case. Proc.Natl.Acad. Sci. U. S. A.2004,101,7258-7263.
Wain, R., Smith, L. J.& Dobson, C. M.. Oxidative refolding of amyloidogenic variants of human lysozyme. J. Mol. Biol.2005,351,662-671.
Wehbi, Z., Perez, M. D., Sanchez, L., Pocovi, C., Barbana, C.& Calvo, M. Effect of heat treatment on denaturation of bovine α-lactalbumin:determination of kinetic and thermodynamic parameters. J. Agric. Food Chem.2005,53,9730-9736.
Welch, K.& Yuan, J. α-synuclein oligomerization:a role for lipids? Trends Neurosci. 2003,26,517-519.
Wickner, S., Maurizi, M. R.& Gottesman, S. Posttranslational quality control:folding, refolding, and degrading proteins. Science 1999,286,1888-1893.
Wright, C. F., Teichmann, S. A., Clarke, J.& Dobson, C. M. The importance of sequence diversity in the aggregation and evolution of proteins. Nature 2005,438, 878-881.
Wyllie, A. H.V Kerr, J. F. R.& Currie, A. R. Cell Death:The significance of apotosis. Int Rev Cytol.1980,68,251-306.
Yang, F., Jr., Zhang, M., Chen, J.& Liang, Y. Structural changes of α-lactalbumin induced by low pH and oleic acid. Biochim. Biophys. Acta 2006a,1764,1389-1396.
Yang, F., Jr., Zhang, M., Zhou, B. R., Chen, J.& Liang, Y. Oleic acid inhibits amyloid formation of the intermediate of a-lactalbumin at moderately acidic pH. J. Mol. Biol.2006b,362,821-834.
Yang, F., Zhou, B. R., Zhang, P., Zhao, Y. F., Chen, J., Liang, Y. Binding of ferulic acid to cytochrome c enhances stability of the protein at physiological pH and inhibits cytochrome c-induced apoptosis. Chem.-Biol. Interact.2007,170,231-243.
Ye, X., Franco, A. A., Santos, H., Nelson, D. M., Kaufman, P. D.& Adams, P. D. Defective S phase chromatin assembly causes DNA damage, activation of the S phase checkpoint, and S phase arrest. Mol. Cell 2003,11,341-351.
Zhao, H., Tuominen, E. K.& Kinnunen, P. K. Formation of amyloid fibers triggered by phosphatidylserine-containing membranes. Biochemistry 2004,43,10302-10307.
Zweig, G.& Block, R. J. Studies on bovine whey proteins. Ⅲ. The preparation of crystalline a-lactalbumin and β-lactoglobulin ferrilactin. Arch. Biochem. Biophys. 1954,51,200-207.
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