6WAQ

Crystal structure of the SARS-CoV-1 RBD bound by the cross-reactive single-domain antibody SARS VHH-72

6WAQ の概要

• エントリーDOI: 10.2210/pdb6waq/pdb
• 分子名称: nanobody SARS VHH-72, Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: sars-cov-1, vhh, nanobody, rbd, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Lama glama; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 71680.57

構造登録者

Wrapp, D.,McLellan, J.S. (登録日: 2020-03-25, 公開日: 2020-04-01, 最終更新日: 2024-10-16)

主引用文献

Wrapp, D.,De Vlieger, D.,Corbett, K.S.,Torres, G.M.,Wang, N.,Van Breedam, W.,Roose, K.,van Schie, L.,Hoffmann, M.,Pohlmann, S.,Graham, B.S.,Callewaert, N.,Schepens, B.,Saelens, X.,McLellan, J.S.
Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies.
Cell, 181:1004-, 2020

PubMed Abstract: Coronaviruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics. Here, we describe the isolation of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs neutralize MERS-CoV or SARS-CoV-1 S pseudotyped viruses, respectively. Crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs interfere with receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S and demonstrate that this cross-reactive VHH neutralizes SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.

PubMed: 32375025
DOI: 10.1016/j.cell.2020.04.031

実験手法

X-RAY DIFFRACTION (2.2 Å)