7M51

B6 Fab fragment bound to the OC43 spike stem helix peptide

Summary for 7M51

• Entry DOI: 10.2210/pdb7m51/pdb
• Descriptor: Spike glycoprotein stem helix peptide, B6 antigen-binding (Fab) fragment heavy chain, B6 antigen-binding (Fab) fragment light chain, ... (5 entities in total)
• Functional Keywords: broadly neutralizing antibody, structural genomics, ssgcid, seattle structural genomics center for infectious disease, antiviral protein, immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 3
• Total formula weight: 49635.21

Authors

Sauer, M.M.,Park, Y.J.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2021-03-22, release date: 2021-05-26, Last modification date: 2023-10-18)

Primary citation

Sauer, M.M.,Tortorici, M.A.,Park, Y.J.,Walls, A.C.,Homad, L.,Acton, O.J.,Bowen, J.E.,Wang, C.,Xiong, X.,de van der Schueren, W.,Quispe, J.,Hoffstrom, B.G.,Bosch, B.J.,McGuire, A.T.,Veesler, D.
Structural basis for broad coronavirus neutralization.
Nat.Struct.Mol.Biol., 28:478-486, 2021

PubMed Abstract: Three highly pathogenic β-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 β-coronavirus spike glycoproteins, including all five human-infecting β-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 β-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-β-coronavirus vaccine.

PubMed: 33981021
DOI: 10.1038/s41594-021-00596-4

Experimental method

X-RAY DIFFRACTION (1.8 Å)