7UIJ

Structural studies of B5-OspC complex

Summary for 7UIJ

• Entry DOI: 10.2210/pdb7uij/pdb
• Descriptor: Monoclonal B5 Fab Heavy Chain, Monoclonal B5 Fab Light Chain, Outer surface protein C, ... (5 entities in total)
• Functional Keywords: fab antibody, ospc borrelia burgdorferi, immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 6
• Total formula weight: 132859.36

Authors

Rudolph, M.J.,Mantis, N. (deposition date: 2022-03-29, release date: 2023-04-05, Last modification date: 2024-11-20)

Primary 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.
Structural Elucidation of a Protective B Cell Epitope on Outer Surface Protein C (OspC) of the Lyme Disease Spirochete, Borreliella burgdorferi.
Mbio, 14:e0298122-e0298122, 2023

PubMed 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 (OspC). 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. 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. The spirochete Borreliella burgdorferi is a causative agent of Lyme disease, the most common tickborne disease in the United States. The spirochete is transmitted to humans during the course of a tick taking a bloodmeal. After B. burgdorferi is deposited into the skin of a human host, it replicates locally and spreads systemically, often resulting in clinical manifestations involving the central nervous system, joints, and/or heart. Antibodies directed against B. burgdorferi's outer surface protein C (OspC) are known to block tick-to-host transmission, as well as dissemination of the spirochete within a mammalian host. In this report, we reveal the first atomic structure of one such antibody in complex with OspC. Our results have implications for the design of a Lyme disease vaccine capable of interfering with multiple stages in B. burgdorferi infection.

PubMed: 36976016
DOI: 10.1128/mbio.02981-22

Experimental method

X-RAY DIFFRACTION (2.701 Å)