Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA.
Department of Medicine, Division of Endocrinology & Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
Curr Atheroscler Rep. 2022 Apr;24(4):277-288. doi: 10.1007/s11883-022-01001-1. Epub 2022 Feb 2.
The binding of high-density lipoprotein (HDL) to its primary receptor, scavenger receptor class B type 1 (SR-B1), is critical for lowering plasma cholesterol levels and reducing cardiovascular disease risk. This review provides novel insights into how the structural elements of SR-B1 drive efficient function with an emphasis on bidirectional cholesterol transport.
We have generated a new homology model of full-length human SR-B1 based on the recent resolution of the partial structures of other class B scavenger receptors. Interrogating this model against previously published observations allows us to generate structurally informed hypotheses about SR-B1's ability to mediate HDL-cholesterol (HDL-C) transport. Furthermore, we provide a structural perspective as to why human variants of SR-B1 may result in impaired HDL-C clearance. A comprehensive understanding of SR-B1's structure-function relationships is critical to the development of therapeutic agents targeting SR-B1 and modulating cardiovascular disease risk.
高密度脂蛋白（HDL）与其主要受体——清道夫受体 B 类 1 型（SR-B1）的结合对于降低血浆胆固醇水平和降低心血管疾病风险至关重要。本综述提供了关于 SR-B1 的结构元件如何驱动其高效功能的新见解，重点是双向胆固醇转运。
我们根据最近其他 B 类清道夫受体部分结构的解析，生成了全长人 SR-B1 的新同源模型。根据之前发表的观察结果对该模型进行研究，使我们能够对 SR-B1 介导 HDL-胆固醇（HDL-C）转运的能力提出基于结构的假设。此外，我们还从结构角度解释了为什么人类 SR-B1 的变体可能导致 HDL-C 清除受损。全面了解 SR-B1 的结构-功能关系对于开发靶向 SR-B1 并调节心血管疾病风险的治疗药物至关重要。
