7XY4

Cryo-EM structure of SARS-CoV-2 spike in complex with VHH21

7XY4 の概要

• エントリーDOI: 10.2210/pdb7xy4/pdb
• EMDBエントリー: 33510
• 分子名称: Spike glycoprotein, VHH21, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: spike, sars-cov-2, coronavirus, glycoprotein, nanobody, vhh21, complex, viral protein, cryo-em, viral protein-immune system complex, 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: 417920.51

構造登録者

Cao, D.,Fan, X.,Zhang, X. (登録日: 2022-05-31, 公開日: 2023-09-13, 最終更新日: 2025-09-03)

主引用文献

Wang, K.,Cao, D.,Liu, L.,Fan, X.,Lin, Y.,He, W.,Zhai, Y.,Xu, P.,Yan, X.,Wang, H.,Zhang, X.,Yang, P.
Identification of a nanobody able to catalyze the destruction of the spike-trimer of SARS-CoV-2.
Front Med, 19:493-506, 2025

PubMed Abstract: Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.

PubMed: 40317451
DOI: 10.1007/s11684-025-1128-4

実験手法

ELECTRON MICROSCOPY (3.3 Å)