Role of apolipoprotein A-II in the structure and remodeling of human high-density lipoprotein (HDL): protein conformational ensemble on HDL.
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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DOI：
10.1021/bi300555d
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发表时间：
2012-06-12
期刊：
影响因子：
2.9
通讯作者：
Gursky O
中科院分区：
文献类型：
--
作者：
Gao X;Yuan S;Jayaraman S;Gursky O
高密度脂蛋白（HDL，或“好胆固醇”）是异质纳米粒子，可以去除多余的细胞胆固醇并防止动脉粥样硬化。 HDL 及其主要蛋白载脂蛋白 A-I (apoA-I) 的心脏保护作用已得到充分证实，但第二种主要蛋白载脂蛋白 A-II (apoA-II) 的功能尚不清楚。在这篇综述中，我们假设了各种 HDL 上的载脂蛋白构象的集合。该组合基于Mei和Atkinson确定的Δ(185–243)apoA-I晶体结构，结合Silva团队在交联研究中提出的apoA-IIdimer的“双发夹”构象，并得到了许多团队数十年来获得的大量低分辨率结构、生物物理和生化数据的支持。所提出的构象集合有助于集成和改进几种现有的 HDL 模型，包括中型圆盘上 apoA-I 的“扣带”构象和球形 HDL 上的“三叶形/四叶形”排列。这个整体提示我们假设内源性apoA-II（i）在含有apoA-I或apoA-II的新生盘状HDL（A-I）和HDL（A-II）转化为含有这两种蛋白质的成熟球形HDL（A-I/A-II）期间帮助赋予脂质表面曲率，并且（ii）通过阻碍HDL（A-I/A-II）的扩张来阻碍HDL（A-I/A-II）的重塑。 apoA-I 构象。此外，我们还报道，虽然内源性 apoA-II 主要在中等大小的球形 HDL（A-I/A-II）上循环，但外源性 apoA-II 可以与任何尺寸的 HDL 结合，从而稍微增加该尺寸并稳定 HDL 组装。这表明内源性和外源性 apoA-II 对 HDL 的影响明显不同。总而言之，现有的结果和模型促使我们假设 apoA-II 对人类 HDL 的新结构和功能作用。
High-density lipoproteins (HDL, or “good cholesterol”) 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 Δ(185–243)apoA-I determined by Mei and Atkinson combined with the “double-hairpin” conformation of apoA-IIdimer proposed in the cross-linking studies by Silva’s 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 “buckle-belt” conformation of apoA-I on the midsize disks and the “trefoil/tetrafoil” 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.
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DOI：
10.1073/pnas.94.23.12291
发表时间：
1997-11-11
影响因子：
11.1
作者：
Borhani, DW;Rogers, DP;Brouillette, CG
通讯作者：
Brouillette, CG
影响因子：
2.9
作者：
CALABRESI, L;MENG, QH;MARCEL, YL
通讯作者：
MARCEL, YL
DOI：
10.1016/j.bbalip.2009.07.004
发表时间：
2009-12-01
影响因子：
4.8
作者：
Gillard, Baiba K.;Lin, Hu-Yu Alice;Pownall, Henry J.
通讯作者：
Pownall, Henry J.
影响因子：
4.4
作者：
Gordon SM;Deng J;Lu LJ;Davidson WS
通讯作者：
Davidson WS
DOI：
10.1016/s0005-2760(96)00102-6
发表时间：
1996-11-11
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM
影响因子：
--
作者：
Calabresi, L;Lucchini, A;Franceschini, G
通讯作者：
Franceschini, G