Structure of scavenger receptor SCARF1 and its interaction with lipoproteins.

IF 6.4 1区 生物学 Q1 BIOLOGY
eLife Pub Date : 2024-11-14 DOI:10.7554/eLife.93428
Yuanyuan Wang, Fan Xu, Guangyi Li, Chen Cheng, Bowen Yu, Ze Zhang, Dandan Kong, Fabao Chen, Yali Liu, Zhen Fang, Longxing Cao, Yang Yu, Yijun Gu, Yongning He
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引用次数: 0

Abstract

SCARF1 (scavenger receptor class F member 1, SREC-1 or SR-F1) is a type I transmembrane protein that recognizes multiple endogenous and exogenous ligands such as modified low-density lipoproteins (LDLs) and is important for maintaining homeostasis and immunity. But the structural information and the mechanisms of ligand recognition of SCARF1 are largely unavailable. Here, we solve the crystal structures of the N-terminal fragments of human SCARF1, which show that SCARF1 forms homodimers and its epidermal growth factor (EGF)-like domains adopt a long-curved conformation. Then, we examine the interactions of SCARF1 with lipoproteins and are able to identify a region on SCARF1 for recognizing modified LDLs. The mutagenesis data show that the positively charged residues in the region are crucial for the interaction of SCARF1 with modified LDLs, which is confirmed by making chimeric molecules of SCARF1 and SCARF2. In addition, teichoic acids, a cell wall polymer expressed on the surface of gram-positive bacteria, are able to inhibit the interactions of modified LDLs with SCARF1, suggesting the ligand binding sites of SCARF1 might be shared for some of its scavenging targets. Overall, these results provide mechanistic insights into SCARF1 and its interactions with the ligands, which are important for understanding its physiological roles in homeostasis and the related diseases.

清道夫受体 SCARF1 的结构及其与脂蛋白的相互作用。
SCARF1(清道夫受体 F 类成员 1,SREC-1 或 SR-F1)是一种 I 型跨膜蛋白,可识别多种内源性和外源性配体,如修饰的低密度脂蛋白(LDL),对维持体内平衡和免疫具有重要作用。但是,SCARF1 的结构信息和配体识别机制在很大程度上是不存在的。在这里,我们解析了人 SCARF1 N 端片段的晶体结构,结果表明 SCARF1 形成同源二聚体,其表皮生长因子(EGF)样结构域呈长曲线构象。然后,我们研究了 SCARF1 与脂蛋白的相互作用,并确定了 SCARF1 上用于识别修饰低密度脂蛋白的区域。诱变数据显示,该区域的正电荷残基是 SCARF1 与修饰的低密度脂蛋白相互作用的关键,这一点通过制作 SCARF1 和 SCARF2 的嵌合分子得到了证实。此外,表达于革兰氏阳性细菌表面的细胞壁聚合物茶酸盐也能抑制修饰后的低密度脂蛋白与 SCARF1 的相互作用,这表明 SCARF1 的配体结合位点可能与其某些清除靶点共享。总之,这些结果提供了有关 SCARF1 及其与配体相互作用的机理认识,这对理解其在体内平衡和相关疾病中的生理作用非常重要。
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来源期刊
eLife
eLife BIOLOGY-
CiteScore
12.90
自引率
3.90%
发文量
3122
审稿时长
17 weeks
期刊介绍: eLife is a distinguished, not-for-profit, peer-reviewed open access scientific journal that specializes in the fields of biomedical and life sciences. eLife is known for its selective publication process, which includes a variety of article types such as: Research Articles: Detailed reports of original research findings. Short Reports: Concise presentations of significant findings that do not warrant a full-length research article. Tools and Resources: Descriptions of new tools, technologies, or resources that facilitate scientific research. Research Advances: Brief reports on significant scientific advancements that have immediate implications for the field. Scientific Correspondence: Short communications that comment on or provide additional information related to published articles. Review Articles: Comprehensive overviews of a specific topic or field within the life sciences.
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