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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

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. Sever...

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Autores principales: Rudolph, Michael J., Davis, Simon A., Haque, H. M. Emranul, Weis, David D., Vance, David J., Piazza, Carol Lyn, Ejemel, Monir, Cavacini, Lisa, Wang, Yang, Mbow, M. Lamine, Gilmore, Robert D., Mantis, Nicholas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10128040/
https://www.ncbi.nlm.nih.gov/pubmed/36976016
http://dx.doi.org/10.1128/mbio.02981-22
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author Rudolph, Michael J.
Davis, Simon A.
Haque, H. M. Emranul
Weis, David D.
Vance, David J.
Piazza, Carol Lyn
Ejemel, Monir
Cavacini, Lisa
Wang, Yang
Mbow, M. Lamine
Gilmore, Robert D.
Mantis, Nicholas J.
author_facet Rudolph, Michael J.
Davis, Simon A.
Haque, H. M. Emranul
Weis, David D.
Vance, David J.
Piazza, Carol Lyn
Ejemel, Monir
Cavacini, Lisa
Wang, Yang
Mbow, M. Lamine
Gilmore, Robert D.
Mantis, Nicholas J.
author_sort Rudolph, Michael J.
collection PubMed
description 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 (OspC(A)). 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 OspC(A). 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.
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spelling pubmed-101280402023-04-26 Structural Elucidation of a Protective B Cell Epitope on Outer Surface Protein C (OspC) of the Lyme Disease Spirochete, Borreliella burgdorferi Rudolph, Michael J. Davis, Simon A. Haque, H. M. Emranul Weis, David D. Vance, David J. Piazza, Carol Lyn Ejemel, Monir Cavacini, Lisa Wang, Yang Mbow, M. Lamine Gilmore, Robert D. Mantis, Nicholas J. mBio Research Article 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 (OspC(A)). 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 OspC(A). 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. American Society for Microbiology 2023-03-28 /pmc/articles/PMC10128040/ /pubmed/36976016 http://dx.doi.org/10.1128/mbio.02981-22 Text en Copyright © 2023 Rudolph et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Rudolph, Michael J.
Davis, Simon A.
Haque, H. M. Emranul
Weis, David D.
Vance, David J.
Piazza, Carol Lyn
Ejemel, Monir
Cavacini, Lisa
Wang, Yang
Mbow, M. Lamine
Gilmore, Robert D.
Mantis, Nicholas J.
Structural Elucidation of a Protective B Cell Epitope on Outer Surface Protein C (OspC) of the Lyme Disease Spirochete, Borreliella burgdorferi
title Structural Elucidation of a Protective B Cell Epitope on Outer Surface Protein C (OspC) of the Lyme Disease Spirochete, Borreliella burgdorferi
title_full Structural Elucidation of a Protective B Cell Epitope on Outer Surface Protein C (OspC) of the Lyme Disease Spirochete, Borreliella burgdorferi
title_fullStr Structural Elucidation of a Protective B Cell Epitope on Outer Surface Protein C (OspC) of the Lyme Disease Spirochete, Borreliella burgdorferi
title_full_unstemmed Structural Elucidation of a Protective B Cell Epitope on Outer Surface Protein C (OspC) of the Lyme Disease Spirochete, Borreliella burgdorferi
title_short Structural Elucidation of a Protective B Cell Epitope on Outer Surface Protein C (OspC) of the Lyme Disease Spirochete, Borreliella burgdorferi
title_sort structural elucidation of a protective b cell epitope on outer surface protein c (ospc) of the lyme disease spirochete, borreliella burgdorferi
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10128040/
https://www.ncbi.nlm.nih.gov/pubmed/36976016
http://dx.doi.org/10.1128/mbio.02981-22
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