7DDP

Cryo-EM structure of human ACE2 and GX/P2V/2017 RBD

7DDP の概要

• エントリーDOI: 10.2210/pdb7ddp/pdb
• EMDBエントリー: 30653
• 分子名称: Angiotensin-converting enzyme 2, Spike protein S1, ZINC ION, ... (4 entities in total)
• 機能のキーワード: pangolin, rbd, ace2, protein binding, hydrolase-viral protein complex, hydrolase/viral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 93733.60

構造登録者

Niu, S.,Wang, J.,Wang, H.W.,Qi, J.X.,Wang, Q.H.,Gao, G.F. (登録日: 2020-10-29, 公開日: 2021-05-19, 最終更新日: 2025-07-02)

主引用文献

Niu, S.,Wang, J.,Bai, B.,Wu, L.,Zheng, A.,Chen, Q.,Du, P.,Han, P.,Zhang, Y.,Jia, Y.,Qiao, C.,Qi, J.,Tian, W.X.,Wang, H.W.,Wang, Q.,Gao, G.F.
Molecular basis of cross-species ACE2 interactions with SARS-CoV-2-like viruses of pangolin origin.
Embo J., 40:e107786-e107786, 2021

PubMed Abstract: Pangolins have been suggested as potential reservoir of zoonotic viruses, including SARS-CoV-2 causing the global COVID-19 outbreak. Here, we study the binding of two SARS-CoV-2-like viruses isolated from pangolins, GX/P2V/2017 and GD/1/2019, to human angiotensin-converting enzyme 2 (hACE2), the receptor of SARS-CoV-2. We find that the spike protein receptor-binding domain (RBD) of pangolin CoVs binds to hACE2 as efficiently as the SARS-CoV-2 RBD in vitro. Furthermore, incorporation of pangolin CoV RBDs allows entry of pseudotyped VSV particles into hACE2-expressing cells. A screen for binding of pangolin CoV RBDs to ACE2 orthologs from various species suggests a broader host range than that of SARS-CoV-2. Additionally, cryo-EM structures of GX/P2V/2017 and GD/1/2019 RBDs in complex with hACE2 show their molecular binding in modes similar to SARS-CoV-2 RBD. Introducing the Q498H substitution found in pangolin CoVs into the SARS-CoV-2 RBD expands its binding capacity to ACE2 homologs of mouse, rat, and European hedgehog. These findings suggest that these two pangolin CoVs may infect humans, highlighting the necessity of further surveillance of pangolin CoVs.

PubMed: 34018203
DOI: 10.15252/embj.2021107786

実験手法

ELECTRON MICROSCOPY (3.4 Å)