7m52 | pdb_00007m52

B6 Fab fragment bound to the HKU4 spike stem helix peptide

spinqualitylabelsall models 7m52, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7m52 is a 3 chain structure with sequence from Mus musculus and Tylonycteris bat coronavirus HKU4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.5Å Ligands: GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SPIKE_BCHK4 S1 region attaches the virion to the cell membrane by interacting with cell receptors, initiating the infection. S2 is a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes (By similarity). 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. See Also Monoclonal Antibodies 3D structures

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