6dc3

RSV prefusion F bound to RSD5 Fab

spinqualitylabelsall models 6dc3, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6dc3 is a 3 chain structure with sequence from Homo sapiens, Human immunodeficiency virus 1, Human respiratory syncytial virus A2 and Unidentified. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.501Å Ligands: NAG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q6N089_HUMAN Publication Abstract from PubMed The respiratory syncytial virus (RSV) fusion (F) glycoprotein is a major target of neutralizing antibodies arising from natural infection, and antibodies that specifically bind to the prefusion conformation of RSV F generally demonstrate the greatest neutralization potency. Prefusion-stabilized RSV F variants have been engineered as vaccine antigens, but crystal structures of these variants have revealed conformational differences in a key antigenic site located at the apex of the trimer, referred to as antigenic site O. Currently, it is unclear if flexibility in this region is an inherent property of prefusion RSV F or if it is related to inadequate stabilization of site O in the engineered variants. Therefore, we set out to investigate the conformational flexibility of antigenic site O, as well as the ability of the human immune system to recognize alternative conformations of this site, by determining crystal structures of prefusion RSV F bound to neutralizing human-derived antibodies AM22 and RSD5. Both antibodies bound with high affinity and were specific for the prefusion conformation of RSV F. Crystal structures of the complexes revealed that the antibodies recognized distinct conformations of antigenic site O, each diverging at a conserved proline residue located in the middle of an alpha-helix. These data suggest that antigenic site O exists as an ensemble of conformations, with individual antibodies recognizing discrete states. Collectively, these results have implications for the refolding of pneumovirus and paramyxovirus fusion proteins and should inform development of prefusion-stabilized RSV F vaccine candidates. Alternative conformations of a major antigenic site on RSV F.,Jones HG, Battles MB, Lin CC, Bianchi S, Corti D, McLellan JS PLoS Pathog. 2019 Jul 15;15(7):e1007944. doi: 10.1371/journal.ppat.1007944., eCollection 2019 Jul. PMID:31306469 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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