7M52

B6 Fab fragment bound to the HKU4 spike stem helix peptide

7M52 の概要

• エントリーDOI: 10.2210/pdb7m52/pdb
• 分子名称: Spike glycoprotein stem helix peptide, B6 antigen-binding (Fab) fragment heavy chain, B6 antigen-binding (Fab) fragment light chain, ... (5 entities in total)
• 機能のキーワード: broadly neutralizing antibody, structural genomics, ssgcid, center for structural genomics of infectious diseases, csgid, antiviral protein, immune system, seattle structural genomics center for infectious disease
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 49476.07

構造登録者

Sauer, M.M.,Park, Y.J.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (登録日: 2021-03-22, 公開日: 2021-05-26, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.5 Å)