9BIF
Fab B11-OspCA complex
Summary for 9BIF
| Entry DOI | 10.2210/pdb9bif/pdb |
| Descriptor | VH-CH1 domain of B11 Fab, VH-VL domain of B11 Fab, Outer surface protein C, ... (6 entities in total) |
| Functional Keywords | anti-ospca monoclonal antibody, immune system |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 24 |
| Total formula weight | 523982.30 |
| Authors | |
| Primary citation | Rudolph, M.J.,Chen, Y.,Vorauer, C.,Vance, D.J.,Piazza, C.L.,Willsey, G.G.,McCarthy, K.,Muriuki, B.,Cavacini, L.A.,Guttman, M.,Mantis, N.J. Structure of a Human Monoclonal Antibody in Complex with Outer Surface Protein C of the Lyme Disease Spirochete, Borreliella burgdorferi. J Immunol., 213:1234-1243, 2024 Cited by PubMed Abstract: Lyme 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 α-helices 1 and 6 and adjacent loops 5 and 6 in one OspCA monomer. In addition, B11 spans the OspCA dimer interface, engaging opposing α-helix 1', α-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. PubMed: 39240158DOI: 10.4049/jimmunol.2400247 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.09 Å) |
Structure validation
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