7RAQ

Crystal structure of CV3-25 Fab bound to SARS-CoV-2 spike stem helix peptide

7RAQ の概要

• エントリーDOI: 10.2210/pdb7raq/pdb
• 分子名称: CV3-25 Fab Heavy Chain, CV3-25 Fab Light Chain, spike stem helix peptide, ... (6 entities in total)
• 機能のキーワード: antibody, fab, sars-cov-2, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 51321.12

構造登録者

Hurlburt, N.K.,Pancera, M. (登録日: 2021-07-02, 公開日: 2022-04-13, 最終更新日: 2024-10-23)

主引用文献

Hurlburt, N.K.,Homad, L.J.,Sinha, I.,Jennewein, M.F.,MacCamy, A.J.,Wan, Y.H.,Boonyaratanakornkit, J.,Sholukh, A.M.,Jackson, A.M.,Zhou, P.,Burton, D.R.,Andrabi, R.,Ozorowski, G.,Ward, A.B.,Stamatatos, L.,Pancera, M.,McGuire, A.T.
Structural definition of a pan-sarbecovirus neutralizing epitope on the spike S2 subunit.
Commun Biol, 5:342-342, 2022

PubMed Abstract: Three betacoronaviruses have crossed the species barrier and established human-to-human transmission causing significant morbidity and mortality in the past 20 years. The most current and widespread of these is SARS-CoV-2. The identification of CoVs with zoonotic potential in animal reservoirs suggests that additional outbreaks could occur. Monoclonal antibodies targeting conserved neutralizing epitopes on diverse CoVs can form the basis for prophylaxis and therapeutic treatments and enable the design of vaccines aimed at providing pan-CoV protection. We previously identified a neutralizing monoclonal antibody, CV3-25 that binds to the SARS-CoV-2 spike, neutralizes the SARS-CoV-2 Beta variant comparably to the ancestral Wuhan Hu-1 strain, cross neutralizes SARS-CoV-1 and binds to recombinant proteins derived from the spike-ectodomains of HCoV-OC43 and HCoV-HKU1. Here, we show that the neutralizing activity of CV3-25 is maintained against the Alpha, Delta, Gamma and Omicron variants of concern as well as a SARS-CoV-like bat coronavirus with zoonotic potential by binding to a conserved linear peptide in the stem-helix region. Negative stain electron microscopy and a 1.74 Å crystal structure of a CV3-25/peptide complex demonstrates that CV3-25 binds to the base of the stem helix at the HR2 boundary to an epitope that is distinct from other stem-helix directed neutralizing mAbs.

PubMed: 35411021
DOI: 10.1038/s42003-022-03262-7

実験手法

X-RAY DIFFRACTION (1.74 Å)