9b8j | pdb_00009b8j

GP38-GnH-DS-Gc in the pre-fusion conformation

spinqualitylabelsall models 9b8j, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9b8j is a 7 chain structure with sequence from Crimean-Congo hemorrhagic fever virus strain IbAr10200 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.4Å Ligands: BMA, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GP_CCHFI Glycoprotein C and glycoprotein N interact with each other and are present at the surface of the virion. They are able to attach the virion to host cell receptors. This attachment induces virion internalization predominantly through clathrin-dependent endocytosis. Also promotes fusion of viral membrane with host endosomal membrane after endocytosis of the virion (By similarity). Publication Abstract from PubMed Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus that can cause severe disease in humans with case fatality rates of 10-40%. Although structures of CCHFV glycoproteins GP38 and Gc have provided insights into viral entry and defined epitopes of neutralizing and protective antibodies, the structure of glycoprotein Gn and its interactions with GP38 and Gc have remained elusive. Here, we used structure-guided protein engineering to produce a stabilized GP38-Gn-Gc heterotrimeric glycoprotein complex (GP38-Gn(H-DS)-Gc). A cryo-EM structure of this complex provides the molecular basis for GP38's association on the viral surface, reveals the structure of Gn, and demonstrates that GP38-Gn restrains the Gc fusion loops in the prefusion conformation, facilitated by an N-linked glycan attached to Gn. Immunization with GP38-Gn(H-DS)-Gc conferred 40% protection against lethal IbAr10200 challenge in mice. These data define the architecture of a GP38-Gn-Gc protomer and provide a template for structure-guided vaccine antigen development. Engineering, structure, and immunogenicity of a Crimean-Congo hemorrhagic fever virus pre-fusion heterotrimeric glycoprotein complex.,McFadden E, Monticelli SR, Wang A, Ramamohan AR, Batchelor TG, Kuehne AI, Bakken RR, Tse AL, Chandran K, Herbert AS, McLellan JS bioRxiv [Preprint]. 2024 Apr 21:2024.04.20.590419. doi: , 10.1101/2024.04.20.590419. PMID:38659837 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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