9LYP

Alpha SARS-CoV-2 spike protein RBD-down in complex with REGN10987 Fab homologue (local refinement)

9LYP の概要

• エントリーDOI: 10.2210/pdb9lyp/pdb
• EMDBエントリー: 63514
• 分子名称: Spike glycoprotein, REGN10987 Fab homologue (Light chain), REGN10987 Fab homologue (Heavy chain), ... (4 entities in total)
• 機能のキーワード: viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 69373.17

構造登録者

Kocharovskaya, M.V.,Pichkur, E.B.,Shenkarev, Z.O.,Lyukmanova, E.N. (登録日: 2025-02-20, 公開日: 2025-04-02)

主引用文献

Kocharovskaya, M.V.,Pichkur, E.B.,Ivannikov, A.D.,Kharlampieva, D.D.,Grafskaia, E.N.,Lyukmanova, E.N.,Kirpichnikov, M.P.,Shenkarev, Z.O.
Structure and dynamics of Alpha B.1.1.7 SARS-CoV-2 S-protein in complex with Fab of neutralizing antibody REGN10987.
Biochem.Biophys.Res.Commun., 755:151558-151558, 2025

PubMed Abstract: One of the approaches for treatment of COVID-19 is a use of neutralizing antibodies (nAbs). The study of the mechanisms by which nAbs recognize different strains of SARS-CoV-2 may facilitate the development of new drugs and vaccines against the coronavirus infection. In this work, we present the 3.1 Å resolution cryo-electron microscopy structure of a full-length trimeric spike-protein (S-protein) of the SARS-CoV-2 Alpha (B.1.1.7) variant in complex with the Fab of the REGN10987 nAb. In the complex, two receptor-binding domains (RBDs) of the S-protein were observed in the 'up' state, whereas third RBD was in the 'down' state. This distinguishes the obtained structure from the complex of Delta (B.1.617.2) S-protein with REGN10987-Fab, where only one RBD was in the 'up' state. Probably some of the substituted residues (K478T, A570D, and S982A) located at the interprotomer interfaces are responsible for the greater Alpha S-protein opening upon the REGN10987-Fab binding. The Fab identically binds to the RBD in the both 'up' and 'down' conformations. The RBD-Fab interaction interface was refined to a resolution of 3.6 Å. The antibody binds to the receptor-binding motif (RBM), which prevents the S-protein from the binding to its receptor, angiotensin-converting enzyme 2 (ACE-2). Comparison with the structures of the Wuhan (wild type) and Delta RBD variants in complex with REGN10987-Fab revealed that the N501Y and T478K/L452R mutations presented in the RBM of the Alpha and Delta variants, respectively, do not affect the mode of the RBD-Fab interaction.

PubMed: 40043614
DOI: 10.1016/j.bbrc.2025.151558

実験手法

ELECTRON MICROSCOPY (3.6 Å)