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Structural Elucidation of a Protective B Cell Epitope on Outer Surface Protein C (OspC) of the Lyme Disease Spirochete, Borreliella burgdorferi
dc.contributor.author | Rudolph, Michael J. | |
dc.contributor.author | Davis, Simon A. | |
dc.contributor.author | Haque, H. M. Emranul | |
dc.contributor.author | Weis, David D. | |
dc.contributor.author | Vance, David J. | |
dc.contributor.author | Piazza, Carol Lyn | |
dc.contributor.author | Ejemel, Monir | |
dc.contributor.author | Cavacini, Lisa | |
dc.contributor.author | Wang, Yang | |
dc.contributor.author | Mbow, M. Lamine | |
dc.contributor.author | Gilmore, Robert D. | |
dc.contributor.author | Mantis, Nicholas J. | |
dc.date.accessioned | 2023-05-30T15:48:27Z | |
dc.date.available | 2023-05-30T15:48:27Z | |
dc.date.issued | 2023-03-28 | |
dc.identifier.citation | Rudolph, M. J., Davis, S. A., Haque, H. M. E., Weis, D. D., Vance, D. J., Piazza, C. L., Ejemel, M., Cavacini, L., Wang, Y., Mbow, M. L., Gilmore, R. D., & Mantis, N. J. (2023). Structural Elucidation of a Protective B Cell Epitope on Outer Surface Protein C (OspC) of the Lyme Disease Spirochete, Borreliella burgdorferi. mBio, 14(2), e0298122. https://doi.org/10.1128/mbio.02981-22 | en_US |
dc.identifier.uri | https://hdl.handle.net/1808/34230 | |
dc.description.abstract | Outer surface protein C (OspC) plays a pivotal role in mediating tick-to-host transmission and infectivity of the Lyme disease spirochete, Borreliella burgdorferi. OspC is a helical-rich homodimer that interacts with tick salivary proteins, as well as components of the mammalian immune system. Several decades ago, it was shown that the OspC-specific monoclonal antibody, B5, was able to passively protect mice from experimental tick-transmitted infection by B. burgdorferi strain B31. However, B5’s epitope has never been elucidated, despite widespread interest in OspC as a possible Lyme disease vaccine antigen. Here, we report the crystal structure of B5 antigen-binding fragments (Fabs) in complex with recombinant OspC type A (OspCA). Each OspC monomer within the homodimer was bound by a single B5 Fab in a side-on orientation, with contact points along OspC’s α-helix 1 and α-helix 6, as well as interactions with the loop between α-helices 5 and 6. In addition, B5’s complementarity-determining region (CDR) H3 bridged the OspC-OspC′ homodimer interface, revealing the quaternary nature of the protective epitope. To provide insight into the molecular basis of B5 serotype specificity, we solved the crystal structures of recombinant OspC types B and K and compared them to OspCA. This study represents the first structure of a protective B cell epitope on OspC and will aid in the rational design of OspC-based vaccines and therapeutics for Lyme disease. | en_US |
dc.publisher | American Society for Microbiology | en_US |
dc.rights | © 2023 Rudolph et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Borreliella burgdorferi | en_US |
dc.subject | Lyme disease | en_US |
dc.subject | X-ray crystallography | en_US |
dc.subject | Monoclonal antibodies | en_US |
dc.subject | Spirochetes | en_US |
dc.subject | Vaccines | en_US |
dc.title | Structural Elucidation of a Protective B Cell Epitope on Outer Surface Protein C (OspC) of the Lyme Disease Spirochete, Borreliella burgdorferi | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Haque, H. M. Emranul | |
kusw.kuauthor | Weis, David D. | |
kusw.kudepartment | Chemistry | en_US |
dc.identifier.doi | 10.1128/mbio.02981-22 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-8687-9535 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-5083-8640 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC10128040 | en_US |
dc.rights.accessrights | openAccess | en_US |