9bif
Fab B11-OspCA complex
Structural highlights
Publication Abstract from PubMedLyme disease is a tick-borne, multisystem infection caused by the spirochete Borreliella burgdorferi. Although Abs have been implicated in the resolution of Lyme disease, the specific B cell epitopes targeted during human infections remain largely unknown. In this study, we characterized and defined the structural epitope of a patient-derived bactericidal monoclonal IgG (B11) against outer surface protein C (OspC), a homodimeric lipoprotein necessary for B. burgdorferi tick-mediated transmission and early-stage colonization of vertebrate hosts. High-resolution epitope mapping was accomplished through hydrogen deuterium exchange-mass spectrometry and X-ray crystallography. Structural analysis of B11 Fab-OspCA complexes revealed the B11 Fabs associated in a 1:1 stoichiometry with the lateral faces of OspCA homodimers such that the Abs are essentially positioned perpendicular to the spirochete's outer surface. B11's primary contacts reside within the membrane-proximal regions of alpha-helices 1 and 6 and adjacent loops 5 and 6 in one OspCA monomer. In addition, B11 spans the OspCA dimer interface, engaging opposing alpha-helix 1', alpha-helix 2', and loop 2-3' in the second OspCA monomer. The B11-OspCA structure is reminiscent of the recently solved mouse transmission blocking monoclonal IgG B5 in complex with OspCA, indicating a mode of engagement with OspC that is conserved across species. In conclusion, we provide a detailed insight into the interaction between a functional human Ab and an immunodominant Lyme disease Ag long considered an important vaccine candidate. Structure of a Human Monoclonal Antibody in Complex with Outer Surface Protein C of the Lyme Disease Spirochete, Borreliella burgdorferi.,Rudolph MJ, Chen Y, Vorauer C, Vance DJ, Piazza CL, Willsey GG, McCarthy K, Muriuki B, Cavacini LA, Guttman M, Mantis NJ J Immunol. 2024 Oct 15;213(8):1234-1243. doi: 10.4049/jimmunol.2400247. PMID:39240158[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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