5y10
SFTSV Gn head domain
Structural highlights
FunctionGP_SFTS Structural component of the virion that interacts with glycoprotein C (By similarity). It shields the hydrophobic fusion loops of the glycoprotein C, preventing premature fusion (By similarity). The glycoprotein protrusions are arranged on an icosahedral lattice, with T=12 triangulation (By similarity). They are able to attach the virion to the host cell receptor CD209/DC-SIGN and to promote fusion of membranes with the late endosome after clathrin-mediated endocytosis of the virion (PubMed:23388721). Plays a role in the packaging of ribonucleoproteins during virus assembly (By similarity).[UniProtKB:P09613][UniProtKB:P21401][1] Structural component of the virion that interacts with glycoprotein N (By similarity). Acts as a class II fusion protein that is activated upon acidification and subsequent repositioning of the glycoprotein N (By similarity). The glycoprotein protrusions are arranged on an icosahedral lattice, with T=12 triangulation (By similarity). They are able to attach the virion to the host cell receptor CD209/DC-SIGN and to promote fusion of membranes with the late endosome after clathrin-mediated endocytosis of the virion (PubMed:23388721).[UniProtKB:P09613][UniProtKB:P21401][2] Publication Abstract from PubMedSevere fever with thrombocytopenia syndrome virus (SFTSV) and Rift Valley fever virus (RVFV) are two arthropod-borne phleboviruses in the Bunyaviridae 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 Bunyaviridae 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 alpha6 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. Structures of phlebovirus glycoprotein Gn and identification of a neutralizing antibody epitope.,Wu Y, Zhu Y, Gao F, Jiao Y, Oladejo BO, Chai Y, Bi Y, Lu S, Dong M, Zhang C, Huang G, Wong G, Li N, Zhang Y, Li Y, Feng WH, Shi Y, Liang M, Zhang R, Qi J, Gao GF Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):E7564-E7573. doi:, 10.1073/pnas.1705176114. Epub 2017 Aug 21. PMID:28827346[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
