7MKL

SARS-CoV-2 Spike in complex with neutralizing Fab SARS2-38 (three down conformation)

7MKL の概要

• エントリーDOI: 10.2210/pdb7mkl/pdb
• EMDBエントリー: 23898 23899
• 分子名称: Spike glycoprotein, SARS2-38 Fv heavy chain, SARS2-38 Fv light chain, ... (5 entities in total)
• 機能のキーワード: glycoprotein, antibody, viral protein-immune system complex, structural genomics, center for structural genomics of infectious diseases, csgid, viral protein/immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 410034.17

構造登録者

Adams, L.J.,Fremont, D.H.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2021-04-24, 公開日: 2021-05-12, 最終更新日: 2025-05-21)

主引用文献

VanBlargan, L.A.,Adams, L.J.,Liu, Z.,Chen, R.E.,Gilchuk, P.,Raju, S.,Smith, B.K.,Zhao, H.,Case, J.B.,Winkler, E.S.,Whitener, B.M.,Droit, L.,Aziati, I.D.,Bricker, T.L.,Joshi, A.,Shi, P.Y.,Creanga, A.,Pegu, A.,Handley, S.A.,Wang, D.,Boon, A.C.M.,Crowe Jr., J.E.,Whelan, S.P.J.,Fremont, D.H.,Diamond, M.S.
A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope.
Immunity, 54:2399-2416.e6, 2021

PubMed Abstract: With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here, we developed a panel of neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) that bound the receptor binding domain of the spike protein at distinct epitopes and blocked virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Although several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by ancestral SARS-CoV-2 strains, others induced escape variants in vivo or lost neutralizing activity against emerging strains. One mAb, SARS2-38, potently neutralized all tested SARS-CoV-2 variants of concern and protected mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engaged a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of neutralizing antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants.

PubMed: 34481543
DOI: 10.1016/j.immuni.2021.08.016

実験手法

ELECTRON MICROSCOPY (3.2 Å)