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基于 cryoEM 的人低密度脂蛋白和结合受体模型。

Model of human low-density lipoprotein and bound receptor based on cryoEM.

机构信息

Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.

出版信息

Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1059-64. doi: 10.1073/pnas.0908004107. Epub 2009 Dec 28.

DOI:10.1073/pnas.0908004107
PMID:20080547
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2798884/
Abstract

Human plasma low-density lipoproteins (LDL), a risk factor for cardiovascular disease, transfer cholesterol from plasma to liver cells via the LDL receptor (LDLr). Here, we report the structures of LDL and its complex with the LDL receptor extracellular domain (LDL.LDLr) at extracellular pH determined by cryoEM. Difference imaging between LDL.LDLr and LDL localizes the site of LDLr bound to its ligand. The structural features revealed from the cryoEM map lead to a juxtaposed stacking model of cholesteryl esters (CEs). High density in the outer shell identifies protein-rich regions that can be accounted for by a single apolipoprotein (apo B-100, 500 kDa) leading to a model for the distribution of its alpha-helix and beta-sheet rich domains across the surface. The structural relationship between the apo B-100 and CEs appears to dictate the structural stability and function of normal LDL.

摘要

人血浆低密度脂蛋白（LDL）是心血管疾病的一个风险因素，它通过 LDL 受体（LDLr）将胆固醇从血浆转移到肝细胞。在这里，我们通过 cryoEM 报告了 LDL 及其与 LDL 受体细胞外结构域（LDL.LDLr）复合物在细胞外 pH 下的结构。通过 LDL.LDLr 和 LDL 之间的差异成像，定位了 LDLr 与其配体结合的部位。从 cryoEM 图谱中揭示的结构特征导致了胆固醇酯（CEs）的并置堆叠模型。外壳的高密度确定了富含蛋白质的区域，这可以由单个载脂蛋白（apo B-100，500 kDa）来解释，这导致了其富含α-螺旋和β-片层的结构域在表面上的分布模型。apo B-100 和 CEs 之间的结构关系似乎决定了正常 LDL 的结构稳定性和功能。

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[3]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

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Structure of triglyceride-rich human low-density lipoproteins according to cryoelectron microscopy.

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