7RPS

B. miyamotoi FbpB complement inhibitory domain

Summary for 7RPS

• Entry DOI: 10.2210/pdb7rps/pdb
• Descriptor: Fibronectin-binding lipoprotein FbpB (2 entities in total)
• Functional Keywords: complement evasion, c1r, borrelia, immune system
• Biological source: Borrelia miyamotoi FR64b
• Total number of polymer chains: 1
• Total formula weight: 19427.79

Authors

Booth, C.E.,Garcia, B.L. (deposition date: 2021-08-04, release date: 2022-04-27, Last modification date: 2023-10-18)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.09 Å)