Structural mechanisms for the recruitment of factor H by Streptococcus pyogenes.

IF 4.3 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Structure Pub Date : 2026-05-07 Epub Date: 2026-03-16 DOI:10.1016/j.str.2026.02.010

Amit Kumar, Kuei-Chen Wang, Partho Ghosh

引用次数: 0

Abstract

The bacterial pathogen Streptococcus pyogenes (Strep A) recruits the complement regulator factor H (FH) to its surface using M proteins and FbaA. However, no conserved FH-binding sequence pattern is evident in these proteins. To address this, we determined the structures of M5 protein, M6 protein, and FbaA fragments complexed with FH domains 6 and 7. M5 and M6 proteins formed dimeric α-helical coiled coils, as expected, while FbaA formed a monomeric three-helix bundle preceded by a loop. Each Strep A protein had a different FH-binding mode, and distinct FH-binding sequence patterns were constructed for each based on substitution mutagenesis. About half of the known 250 Strep A strains were identified to have FH-binding patterns, with the majority due to FbaA as compared to M or M-like Enn proteins. Our structural and functional elucidation of the mechanism of FH recruitment is applicable to the precise investigation of its role in Strep A virulence.

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化脓性链球菌募集因子H的结构机制。

细菌病原体化脓性链球菌（Streptococcus pyogenes，简称Strep A）利用M蛋白和FbaA将补体调节因子H（补体调节因子H）募集到自身表面。然而，在这些蛋白中没有明显的保守的fh结合序列模式。为了解决这个问题，我们确定了M5蛋白、M6蛋白和FbaA片段与FH结构域6和7的复合物的结构。M5和M6蛋白形成了二聚体α-螺旋线圈，而FbaA形成了一个单体的三螺旋束，前面有一个环。每种Strep A蛋白具有不同的fh结合模式，并基于置换诱变构建了不同的fh结合序列模式。在已知的250株甲型链球菌中，约有一半被鉴定出具有fh结合模式，与M或M样Enn蛋白相比，大多数是由于FbaA。我们对FH募集机制的结构和功能阐明适用于其在甲型链球菌毒力中的精确研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Structure 生物-生化与分子生物学

CiteScore

8.90

自引率

1.80%

发文量

155

审稿时长

3-8 weeks

期刊介绍： Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome. In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.