7m5e

MERS-CoV S bound to the broadly neutralizing B6 Fab fragment (C3 refinement)

spinqualitylabelsall models 7m5e, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.5Å Ligands: BMA, FOL, MAN, NAG, SIA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Three highly pathogenic beta-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying antibodies with broad neutralizing activity, we isolated a monoclonal antibody, termed B6, that cross-reacts with eight beta-coronavirus spike glycoproteins, including all five human-infecting beta-coronaviruses. B6 broadly neutralizes entry of pseudotyped viruses from lineages A and C, but not from lineage B, and the latter includes SARS-CoV and SARS-CoV-2. Cryo-EM, X-ray crystallography and membrane fusion assays reveal that B6 binds to a conserved cryptic epitope located in the fusion machinery. The data indicate that antibody binding sterically interferes with the spike conformational changes leading to membrane fusion. Our data provide a structural framework explaining B6 cross-reactivity with beta-coronaviruses from three lineages, along with a proof of concept for antibody-mediated broad coronavirus neutralization elicited through vaccination. This study unveils an unexpected target for next-generation structure-guided design of a pan-beta-coronavirus vaccine. Structural basis for broad coronavirus neutralization.,Sauer MM, Tortorici MA, Park YJ, Walls AC, Homad L, Acton OJ, Bowen JE, Wang C, Xiong X, de van der Schueren W, Quispe J, Hoffstrom BG, Bosch BJ, McGuire AT, Veesler D Nat Struct Mol Biol. 2021 May 12. pii: 10.1038/s41594-021-00596-4. doi:, 10.1038/s41594-021-00596-4. PMID:33981021 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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