6IEB

Structure of RVFV Gn and human monoclonal antibody R15

Summary for 6IEB

• Entry DOI: 10.2210/pdb6ieb/pdb
• Descriptor: R15 H chain, R15 L chain, NSmGnGc, ... (4 entities in total)
• Functional Keywords: rvfv, antibody, structural protein, structural protein-immune system complex, structural protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 160198.23

Authors

Wang, Q.H.,Wu, Y.,Gao, F.,Qi, J.X.,Gao, G.F. (deposition date: 2018-09-13, release date: 2019-04-10, Last modification date: 2024-10-30)

Primary citation

Wang, Q.,Ma, T.,Wu, Y.,Chen, Z.,Zeng, H.,Tong, Z.,Gao, F.,Qi, J.,Zhao, Z.,Chai, Y.,Yang, H.,Wong, G.,Bi, Y.,Wu, L.,Shi, R.,Yang, M.,Song, J.,Jiang, H.,An, Z.,Wang, J.,Yilma, T.D.,Shi, Y.,Liu, W.J.,Liang, M.,Qin, C.,Gao, G.F.,Yan, J.
Neutralization mechanism of human monoclonal antibodies against Rift Valley fever virus.
Nat Microbiol, 4:1231-1241, 2019

PubMed Abstract: Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that causes substantial morbidity and mortality in livestock and humans. To date, there are no licensed human vaccines or therapeutics available. Here, we report the isolation of monoclonal antibodies from a convalescent patient, targeting the RVFV envelope proteins Gn and Gc. The Gn-specific monoclonal antibodies exhibited much higher neutralizing activities in vitro and protection efficacies in mice against RVFV infection, compared to the Gc-specific monoclonal antibodies. The Gn monoclonal antibodies were found to interfere with soluble Gn binding to cells and prevent infection by blocking the attachment of virions to host cells. Structural analysis of Gn complexed with four Gn-specific monoclonal antibodies resulted in the definition of three antigenic patches (A, B and C) on Gn domain I. Both patches A and B are major neutralizing epitopes. Our results highlight the potential of antibody-based therapeutics and provide a structure-based rationale for designing vaccines against RVFV.

PubMed: 30936489
DOI: 10.1038/s41564-019-0411-z

Experimental method

X-RAY DIFFRACTION (2.409 Å)