7RPR

Borrelia miyamotoi FbpA complement inhibitory domain

7RPR の概要

• エントリーDOI: 10.2210/pdb7rpr/pdb
• 分子名称: Fibronectin-binding lipoprotein FbpA (2 entities in total)
• 機能のキーワード: complement evasion, c1r, borrelia, immune system
• 由来する生物種: Borrelia miyamotoi FR64b
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36176.81

構造登録者

Booth, C.E.,Garcia, B.L. (登録日: 2021-08-04, 公開日: 2022-04-27, 最終更新日: 2023-10-18)

主引用文献

Booth Jr., C.E.,Powell-Pierce, A.D.,Skare, J.T.,Garcia, B.L.
Borrelia miyamotoi FbpA and FbpB Are Immunomodulatory Outer Surface Lipoproteins With Distinct Structures and Functions.
Front Immunol, 13:886733-886733, 2022

PubMed Abstract: Pathogens that traffic in the blood of their hosts must employ mechanisms to evade the host innate immune system, including the complement cascade. The Lyme disease spirochete, , has evolved numerous outer membrane lipoproteins that interact directly with host proteins. Compared to Lyme disease-associated spirochetes, relatively little is known about how an emerging tick-borne spirochetal pathogen, , utilizes surface lipoproteins to interact with a human host. expresses the multifunctional lipoprotein, BBK32, that inhibits the classical pathway of complement through interaction with the initiating protease C1r, and also interacts with fibronectin using a separate intrinsically disordered domain. encodes two separate orthologs denoted and ; however, the activities of these proteins are unknown. Here, we show that FbpA binds human fibronectin in a manner similar to BBK32, whereas FbpB does not. FbpA and FbpB both bind human complement C1r and protect a serum-sensitive strain from complement-mediated killing, but surprisingly, differ in their ability to recognize activated C1r versus zymogen states of C1r. To better understand the observed differences in C1r recognition and inhibition properties, high-resolution X-ray crystallography structures were solved of the C1r-binding regions of FbpA and FbpB at 1.9Å and 2.1Å, respectively. Collectively, these data suggest that FbpA and FbpB have partially overlapping functions but are functionally and structurally distinct. The data presented herein enhances our overall understanding of how bloodborne pathogens interact with fibronectin and modulate the complement system.

PubMed: 35693799
DOI: 10.3389/fimmu.2022.886733

実験手法

X-RAY DIFFRACTION (1.9 Å)