5Y11

SFTSV GN with neutralizing antibody MAb4-5

Summary for 5Y11

• Entry DOI: 10.2210/pdb5y11/pdb
• Descriptor: MAb 4-5 heavy chain, MAb 4-5 light chain, Membrane glycoprotein polyprotein, ... (6 entities in total)
• Functional Keywords: sftsv, gn, neutralizing antibody, phlebovirus, viral protein, immune system-viral system complex, immune system/viral system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 85468.61

Authors

Wu, Y.,Gao, F.,Qi, J.X.,Chai, Y.,Gao, G.F. (deposition date: 2017-07-19, release date: 2017-09-13, Last modification date: 2020-07-29)

Primary citation

Wu, Y.,Zhu, Y.H.,Gao, F.,Jiao, Y.J.,Oladejo, B.O.,Chai, Y.,Bi, Y.H.,Lu, S.,Dong, M.Q.,Zhang, C.,Huang, G.M.,Wong, G.,Li, N.,Zhang, Y.F.,Li, Y.,Feng, W.H.,Shi, Y.,Liang, M.F.,Zhang, R.G.,Qi, J.X.,Gao, G.F.
Structures of phlebovirus glycoprotein Gn and identification of a neutralizing antibody epitope
Proc. Natl. Acad. Sci. U.S.A., 114:E7564-E7573, 2017

PubMed Abstract: Severe fever with thrombocytopenia syndrome virus (SFTSV) and Rift Valley fever virus (RVFV) are two arthropod-borne phleboviruses in the family, which cause severe illness in humans and animals. Glycoprotein N (Gn) is one of the envelope proteins on the virus surface and is a major antigenic component. Despite its importance for virus entry and fusion, the molecular features of the phleboviruse Gn were unknown. Here, we present the crystal structures of the Gn head domain from both SFTSV and RVFV, which display a similar compact triangular shape overall, while the three subdomains (domains I, II, and III) making up the Gn head display different arrangements. Ten cysteines in the Gn stem region are conserved among phleboviruses, four of which are responsible for Gn dimerization, as revealed in this study, and they are highly conserved for all members in Therefore, we propose an anchoring mode on the viral surface. The complex structure of the SFTSV Gn head and human neutralizing antibody MAb 4-5 reveals that helices α6 in subdomain III is the key component for neutralization. Importantly, the structure indicates that domain III is an ideal region recognized by specific neutralizing antibodies, while domain II is probably recognized by broadly neutralizing antibodies. Collectively, Gn is a desirable vaccine target, and our data provide a molecular basis for the rational design of vaccines against the diseases caused by phleboviruses and a model for bunyavirus Gn embedding on the viral surface.

PubMed: 28827346
DOI: 10.1073/pnas.1705176114

Experimental method

X-RAY DIFFRACTION (2.1 Å)