Crystal Structure of C-terminal Truncated Apolipoprotein A-I Reveals the Assembly of High Density Lipoprotein (HDL) by Dimerization
Crystal Structure of C-terminal Truncated Apolipoprotein A-I Reveals the Assembly of High Density Lipoprotein (HDL) by Dimerization
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DOI：
10.1074/jbc.m111.260422
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发表时间：
2011-11-04
影响因子：
4.8
通讯作者：
Atkinson, David
中科院分区：
文献类型：
--
作者：
Mei, Xiaohu;Atkinson, David
载脂蛋白A-I（apoA-I）在血浆高密度脂蛋白（HDL）中起着重要的结构和功能作用，HDL负责胆固醇的逆向转运。然而，HDL组装和功能的分子理解仍然是谜。本文报道的Delta（185-243）apoA-I的2.2埃晶体结构表明它形成半圆二聚体。二聚体的骨架由两个伸长的反平行脯氨酸扭结螺旋（5个AB串联重复）组成。每个分子的N-末端结构域与螺旋相关配偶体的螺旋C-末端区域形成四螺旋束。中心区域形成了一个灵活的域与两个反平行的螺旋连接束在每个端部。基于螺旋重复序列的双结构域二聚体结构表明apoA-I在盘状HDL颗粒形成中的作用。此外，结构表明可能与卵磷脂胆固醇酰基转移酶的相互作用，并可能揭示米兰，巴黎，和鳍突变的影响的分子细节。
Apolipoprotein A-I (apoA-I) plays important structural and functional roles in plasma high density lipoprotein (HDL) that is responsible for reverse cholesterol transport. However, a molecular understanding of HDL assembly and function remains enigmatic. The 2.2-angstrom crystal structure of Delta(185-243) apoA-I reported here shows that it forms a half-circle dimer. The backbone of the dimer consists of two elongated antiparallel proline-kinked helices (five AB tandem repeats). The N-terminal domain of each molecule forms a four-helix bundle with the helical C-terminal region of the symmetry-related partner. The central region forms a flexible domain with two antiparallel helices connecting the bundles at each end. The two-domain dimer structure based on helical repeats suggests the role of apoA-I in the formation of discoidal HDL particles. Furthermore, the structure suggests the possible interaction with lecithin-cholesterol acyltransferase and may shed light on the molecular details of the effect of the Milano, Paris, and Fin mutations.