APOBEC3C的研究进展
|
摘要
与APOBEC3s其他成员相比,APOBEC3C是特殊的,因为APOBEC3C的抗病毒和抗逆转录元件的功能较弱。APOBEC3C只有一个与锌离子协调的胞嘧啶脱氨酶域,并根据氨基酸特异性被划分为A3Z2。与APOBEC3G相比,APOBEC3C引发HIV-1DNA上胞嘧啶脱氨基的数目较少,所以降低了其抑制HIV-1逆转录及整合的能力。APOBEC3C可在靶细胞引起G→A突变,而G→A突变能导致病毒多样性却无法抑制病毒复制。人类APOBEC3C编码的S188I多态性增强了蛋白质的酶促活性及其抑制HIV-1的能力。另外,人类APOEC3C酶的二聚化增加了单链DNA的持续合成能力,可导致体外和细胞内逆转录过程中的大量突变。APOBEC3C已在灵长类的正选择下进化,是病毒在天然感染过程中必须对抗的重要屏障。因此,对APOBEC3C的研究可为抗病毒和抗癌症的治疗设计提供一些思路。
APOBEC3 C is special as it has only weak antiviral functions and weakly restricts retroelements compared to other APOBEC3 s. APOBEC3 has only one cytidine deaminase domain which coordinates a zinc ion,and then is classified to A3 Z2 according to the amino acid specificity. APOBEC3 C induces less cytidine deamination in HIV-1 DNA than APOBEC3 G and has reduced ability to inhibit HIV-1 reverse transcription and integration compared to APOBEC3 G. APOBEC3 C induces G-to-A mutation that cannot block viral replications but contribute more to viral diversity. A single nucleotide polymorphism in human APOBEC3 C,a change from serine to isoleucine at position 188,results in increased enzymatic activity and potent antiviral activity against HIV-1. Dimerization of human APOBEC3 C increases the ability of continuous synthesis of single-stranded DNA,resulting in higher levels of mutation during reverse transcription in vitro and in cells. APOBEC3 C has evolved under positive selection in primates,and it is an important barrier that must be countered by the virus during natural infections. Therefore,research on APOBEC3 C may provide some ideas for anti-retroviral and anti-cancer therapeutic design.
APOBEC3 C is special as it has only weak antiviral functions and weakly restricts retroelements compared to other APOBEC3 s. APOBEC3 has only one cytidine deaminase domain which coordinates a zinc ion,and then is classified to A3 Z2 according to the amino acid specificity. APOBEC3 C induces less cytidine deamination in HIV-1 DNA than APOBEC3 G and has reduced ability to inhibit HIV-1 reverse transcription and integration compared to APOBEC3 G. APOBEC3 C induces G-to-A mutation that cannot block viral replications but contribute more to viral diversity. A single nucleotide polymorphism in human APOBEC3 C,a change from serine to isoleucine at position 188,results in increased enzymatic activity and potent antiviral activity against HIV-1. Dimerization of human APOBEC3 C increases the ability of continuous synthesis of single-stranded DNA,resulting in higher levels of mutation during reverse transcription in vitro and in cells. APOBEC3 C has evolved under positive selection in primates,and it is an important barrier that must be countered by the virus during natural infections. Therefore,research on APOBEC3 C may provide some ideas for anti-retroviral and anti-cancer therapeutic design.
引文
[1]Wittkopp CJ,Adolph MB,Wu Li,et al.A single nucleotide polymorphism in human APOBEC3C enhances restriction of lentiviruses[J].PLoS Pathogens,2016,12(10):e1005865.
[2]Perkov i M,Schmidt S,Marino D,et al.Species-specific inhibition of APOBEC3C by the prototype foamy virus protein bet[J].JBiolog Chem,2009,284(9):5819-5826.
[3]Stauch B,Hofmann H,Perkovic M,et al.Model structure of APO-BEC3C reveals a binding pocket modulating ribonucleic acid interaction required for encapsidation[J].Proc Natl Acad Sci U S A,2009,106(29):12079-12084.
[4]Adolph MB,Ara A,Feng Y,et al.Cytidine deaminase efficiency of the lentiviral viral restriction factor APOBEC3C correlates with dimerization[J].Nucleic Acids Res,2017,45(6):3378-3394.
[5]Desimmie BA,Burdick RC,Izumi T,et al.APOBEC3 proteins can copackage and comutate HIV-1 genomes[J].Nucleic Acids Res,2016,44(16):7848-7865.
[6]Aydin H,Taylor MW,Lee JE.Structure-guided analysis of the human APOBEC3-HIV restrictome[J].Structure,2014,22(5):668-684.
[7]Siriwardena SU,Chen K,Bhagwat AS.The functions and malfunctions of AID/APOBEC family deaminases:the known knowns and the known unknowns[J].Chem Rev,2016,116(20):12688-12710.
[8]Bourara K,Liegler TJ,Grant RM.Target cell APOBEC3C can induce limited G-to-A mutation in HIV-1[J].PLoS Pathogens,2007,3(10):1477-1485.
[9]Vasudevan AA,Smits SH,H9ppner A,et al.Structural features of antiviral DNA cytidine deaminases[J].Biolog Chem,2013,394(11):1357-1370.
[10]Li J,Chen Y,Li M,et al.APOBEC3 multimerization correlates with HIV-1 packaging and restriction activity in living cells[J].JMol Biol,2014,426(6):1296-1307.
[11]Wang Tao,Zhang Wenyan,Tian Chunjuan,et al.Distinct viral determinants for the packaging of human cytidine deaminases APO-BEC3G and APOBEC3C[J].Virology,2008,377(1):71-79.
[12]Desimmie BA,Delviks-Frankenberrry KA,Burdick RC,et al.Multiple APOBEC3 restriction factors for HIV-1 and one vif to rule them all[J].J Mol Biol,2014,426(6):1220-1245.
[13]Zhang Z,Gu Q,Jaguva Vasudevan AA,et al.Vif proteins from diverse HIV/SIV lineages have distinct binding sites in A3C[J].JVirol,2016,90(22):10193-10208.
[14]Langlois MA,Beale RC,Conticello SG,et al.Mutational comparison of the single-domained APOBEC3C and double-domained APOBEC3F/G anti-retroviral cytidine deaminases provides insight into their DNA target site specificities[J].Nucleic Acids Res,2005,33(6):1913-1923.
[15]Shandilya SM,Bohn MF,Schiffer CA.A computational analysis of the structural determinants of APOBEC3's catalytic activity and vulnerability to HIV-1 Vif[J].Virology,2014,471-473:105-116.
[16]Vasudevan AA,Hofmann H,Willbold D,et al.Enhancing the catalytic deamination activity of APOBEC3C is insufficient to inhibit vif-deficient HIV-1[J].J Mol Biol,2017,429(8):1171-1191.
[17]Greenwood EJ,Matheson NJ,Wals K,et al.Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants[J].Elife,2016,5:e18296.
[18]Li D,Liu J,Kang F,et al.Core-APOBEC3C chimerical protein inhibits hepatitis B virus replication[J].J Biochem,2011,150(4):371-374.
[19]Horn AV,Klawitter S,Held U,et al.Human LINE-1 restriction by APOBEC3C is deaminase independent and mediated by an ORF1p interaction that affects LINE reverse transcriptase activity[J].Nucleic Acids Res,2014,42(1):396-416.
[20]Ariumi Y.Guardian of the human genome:host defense mechanisms against LINE-1 retrotransposition[J].Front Chem,2016,4(275):28.
[2]Perkov i M,Schmidt S,Marino D,et al.Species-specific inhibition of APOBEC3C by the prototype foamy virus protein bet[J].JBiolog Chem,2009,284(9):5819-5826.
[3]Stauch B,Hofmann H,Perkovic M,et al.Model structure of APO-BEC3C reveals a binding pocket modulating ribonucleic acid interaction required for encapsidation[J].Proc Natl Acad Sci U S A,2009,106(29):12079-12084.
[4]Adolph MB,Ara A,Feng Y,et al.Cytidine deaminase efficiency of the lentiviral viral restriction factor APOBEC3C correlates with dimerization[J].Nucleic Acids Res,2017,45(6):3378-3394.
[5]Desimmie BA,Burdick RC,Izumi T,et al.APOBEC3 proteins can copackage and comutate HIV-1 genomes[J].Nucleic Acids Res,2016,44(16):7848-7865.
[6]Aydin H,Taylor MW,Lee JE.Structure-guided analysis of the human APOBEC3-HIV restrictome[J].Structure,2014,22(5):668-684.
[7]Siriwardena SU,Chen K,Bhagwat AS.The functions and malfunctions of AID/APOBEC family deaminases:the known knowns and the known unknowns[J].Chem Rev,2016,116(20):12688-12710.
[8]Bourara K,Liegler TJ,Grant RM.Target cell APOBEC3C can induce limited G-to-A mutation in HIV-1[J].PLoS Pathogens,2007,3(10):1477-1485.
[9]Vasudevan AA,Smits SH,H9ppner A,et al.Structural features of antiviral DNA cytidine deaminases[J].Biolog Chem,2013,394(11):1357-1370.
[10]Li J,Chen Y,Li M,et al.APOBEC3 multimerization correlates with HIV-1 packaging and restriction activity in living cells[J].JMol Biol,2014,426(6):1296-1307.
[11]Wang Tao,Zhang Wenyan,Tian Chunjuan,et al.Distinct viral determinants for the packaging of human cytidine deaminases APO-BEC3G and APOBEC3C[J].Virology,2008,377(1):71-79.
[12]Desimmie BA,Delviks-Frankenberrry KA,Burdick RC,et al.Multiple APOBEC3 restriction factors for HIV-1 and one vif to rule them all[J].J Mol Biol,2014,426(6):1220-1245.
[13]Zhang Z,Gu Q,Jaguva Vasudevan AA,et al.Vif proteins from diverse HIV/SIV lineages have distinct binding sites in A3C[J].JVirol,2016,90(22):10193-10208.
[14]Langlois MA,Beale RC,Conticello SG,et al.Mutational comparison of the single-domained APOBEC3C and double-domained APOBEC3F/G anti-retroviral cytidine deaminases provides insight into their DNA target site specificities[J].Nucleic Acids Res,2005,33(6):1913-1923.
[15]Shandilya SM,Bohn MF,Schiffer CA.A computational analysis of the structural determinants of APOBEC3's catalytic activity and vulnerability to HIV-1 Vif[J].Virology,2014,471-473:105-116.
[16]Vasudevan AA,Hofmann H,Willbold D,et al.Enhancing the catalytic deamination activity of APOBEC3C is insufficient to inhibit vif-deficient HIV-1[J].J Mol Biol,2017,429(8):1171-1191.
[17]Greenwood EJ,Matheson NJ,Wals K,et al.Temporal proteomic analysis of HIV infection reveals remodelling of the host phosphoproteome by lentiviral Vif variants[J].Elife,2016,5:e18296.
[18]Li D,Liu J,Kang F,et al.Core-APOBEC3C chimerical protein inhibits hepatitis B virus replication[J].J Biochem,2011,150(4):371-374.
[19]Horn AV,Klawitter S,Held U,et al.Human LINE-1 restriction by APOBEC3C is deaminase independent and mediated by an ORF1p interaction that affects LINE reverse transcriptase activity[J].Nucleic Acids Res,2014,42(1):396-416.
[20]Ariumi Y.Guardian of the human genome:host defense mechanisms against LINE-1 retrotransposition[J].Front Chem,2016,4(275):28.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |