Role of Apolipoprotein A-II in the Structure and Remodeling of Human High-Density Lipoprotein (HDL): Protein Conformational Ensemble on HDL

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• 作者：Xuan Gao ; Shujun Yuan ; Shobini Jayaraman ; Olga Gursky
• 刊名：Biochemistry
• 出版年：2012
• 出版时间：June 12, 2012
• 年：2012
• 卷：51
• 期：23
• 页码：4633-4641
• 全文大小：331K
• 年卷期：v.51,no.23(June 12, 2012)
• ISSN：1520-4995

文摘

High-density lipoproteins (HDL, or 鈥済ood cholesterol鈥? are heterogeneous nanoparticles that remove excess cell cholesterol and protect against atherosclerosis. The cardioprotective action of HDL and its major protein, apolipoprotein A-I (apoA-I), is well-established, yet the function of the second major protein, apolipoprotein A-II (apoA-II), is less clear. In this review, we postulate an ensemble of apolipoprotein conformations on various HDL. This ensemble is based on the crystal structure of 螖(185鈥?43)apoA-I determined by Mei and Atkinson combined with the 鈥渄ouble-hairpin鈥?conformation of apoA-II_dimer proposed in the cross-linking studies by Silva鈥檚 team, and is supported by the wide array of low-resolution structural, biophysical, and biochemical data obtained by many teams over decades. The proposed conformational ensemble helps integrate and improve several existing HDL models, including the 鈥渂uckle-belt鈥?conformation of apoA-I on the midsize disks and the 鈥渢refoil/tetrafoil鈥?arrangement on spherical HDL. This ensemble prompts us to hypothesize that endogenous apoA-II (i) helps confer lipid surface curvature during conversion of nascent discoidal HDL(A-I) and HDL(A-II) containing either apoA-I or apoA-II to mature spherical HDL(A-I/A-II) containing both proteins, and (ii) hinders remodeling of HDL(A-I/A-II) by hindering the expansion of the apoA-I conformation. Also, we report that, although endogenous apoA-II circulates mainly on the midsize spherical HDL(A-I/A-II), exogenous apoA-II can bind to HDL of any size, thereby slightly increasing this size and stabilizing the HDL assembly. This suggests distinctly different effects of the endogenous and exogenous apoA-II on HDL. Taken together, the existing results and models prompt us to postulate a new structural and functional role of apoA-II on human HDL.