7DDP

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

Summary for 7DDP

• Entry DOI: 10.2210/pdb7ddp/pdb
• EMDB information: 30653
• Descriptor: Angiotensin-converting enzyme 2, Spike protein S1, ZINC ION, ... (4 entities in total)
• Functional Keywords: pangolin, rbd, ace2, protein binding, hydrolase-viral protein complex, hydrolase/viral protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 93733.60

Authors

Niu, S.,Wang, J.,Wang, H.W.,Qi, J.X.,Wang, Q.H.,Gao, G.F. (deposition date: 2020-10-29, release date: 2021-05-19, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.4 Å)