期刊
COMMUNICATIONS BIOLOGY
卷 3, 期 1, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s42003-019-0749-z
关键词
-
资金
- National Institutes of Health (NIH) [HL131288, HL122416, HL071818, CA221289, GM007767, HL125242, GM095832, GM105942, GM105920, GM067260]
- American Heart Association [15POST24870001, 16POST27760002]
- American Foundation for Pharmaceutical Education fellowship
- Waters Corporation
- American Foundation for Pharmaceutical Education
- MedImmune
- Walther Cancer Foundation
Lecithin:cholesterol acyltransferase (LCAT) catalyzes a critical step of reverse cholesterol transport by esterifying cholesterol in high density lipoprotein (HDL) particles. LCAT is activated by apolipoprotein A-I (ApoA-I), which forms a double belt around HDL, however the manner in which LCAT engages its lipidic substrates and ApoA-I in HDL is poorly understood. Here, we used negative stain electron microscopy, crosslinking, and hydrogen-deuterium exchange studies to refine the molecular details of the LCAT-HDL complex. Our data are consistent with LCAT preferentially binding to the edge of discoidal HDL near the boundary between helix 5 and 6 of ApoA-I in a manner that creates a path from the lipid bilayer to the active site of LCAT. Our results provide not only an explanation why LCAT activity diminishes as HDL particles mature, but also direct support for the anti-parallel double belt model of HDL, with LCAT binding preferentially to the helix 4/6 region. Manthei et al. use negative stain electron microscopy, crosslinking, and hydrogen-deuterium exchange to better define the lecithin:cholesterol acyltransferase (LCAT)-high density lipoprotein (HDL) complex. They provide a rationale for why LCAT activity diminishes as HDL particles mature into a spherical shape.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据