In situ AFM imaging of apolipoprotein A-I directly derived from plasma HDL

In situ AFM imaging of apolipoprotein A-I directly derived from plasma HDL
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DOI:
10.1016/j.atherosclerosis.2017.02.022
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发表时间:
2017-04-01
期刊:
影响因子:
5.3
通讯作者:
Chen, Yong
Chen, Yong
中科院分区:
医学2区
文献类型:
--
作者:
Gan, Chaoye;Wang, Zhexuan;Chen, Yong

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背景和目标:血浆脂蛋白中的主要载脂蛋白对脂蛋白的结构完整性和生理功能起着至关重要的作用。载脂蛋白A-I(apoA-I)是高密度脂蛋白(HDL)的主要载脂蛋白,目前已建立了十余种结构模型。在这些模型中,apoA-I应该以环状形式组织。迄今为止,然而,没有直接的证据在生理condition.Methods:在这里,原子力显微镜(AFM)被用来在原位可视化apoA-I的组织,这是暴露通过耗尽的脂质成分的血浆HDL预固定在功能化云母片。首次发现了环形粗构造和三个细构造用AFM直接观察并定量测定了血浆HDL中具有清道夫受体结合能力的apoA-I的新月形、缺口“O”形和圆括号形结构。这三个详细的结构可能代表了HDL的脂质成分被耗尽的不同程度。HDL的脂质耗竭数据可能提供线索,了解脂质插入HDL.Conclusions:这些数据提供了重要的信息,为了解血浆HDL的结构/成熟。此外,他们提出了一个强大的方法,直接可视化血浆脂蛋白的主要载脂蛋白或脂蛋白样脂质蛋白复合物的蛋白质组分。(c)2017年爱思唯尔B。V.保留所有权利。
Background and aims: The major apolipoproteins of plasma lipoproteins play vital roles in the structural integrity and physiological functions of lipoproteins. More than ten structural models of apolipoprotein A-l (apoA-I), the major apolipoprotein of high-density lipoprotein (HDL), have been developed successively. In these models, apoA-I was supposed to organize in a ring-shaped form. To date, however, there is no direct evidence under physiological condition.Methods: Here, atomic force microscopy (AFM) was used to in situ visualize the organization of apoA-I, which was exposed via depletion of the lipid component of plasma HDL pre-immobilized on functionalized mica sheets.Results: For the first time, the ring-shaped coarse structure and three detailed structures (crescentshaped, gapped "O" -shaped, and parentheses-shaped structures, respectively) of apoA-I in plasma HDL, which have the ability of binding scavenger receptors, were directly observed and quantitatively measured by AFM. The three detailed structures probably represent the different extents to which the lipid component of HDL was depleted. Data on lipid depletion of HDL may provide clues to understand lipid insertion of HDL.Conclusions: These data provide important information for the understanding of the structure/maturation of plasma HDL. Moreover, they suggest a powerful method for directly visualizing the major apolipoproteins of plasma lipoproteins or the protein component of lipoprotein-like lipid-protein complexes. (c) 2017 Elsevier B. V. All rights reserved.