8XZB

The structure of fox ACE2 and SARS-CoV RBD complex

Summary for 8XZB

• Entry DOI: 10.2210/pdb8xzb/pdb
• EMDB information: 38792
• Descriptor: Angiotensin-converting enzyme, Spike protein S1, ZINC ION (3 entities in total)
• Functional Keywords: fox ace2 sars-cov rbd, viral protein
• Biological source: Vulpes vulpes (red fox); More
• Total number of polymer chains: 2
• Total formula weight: 96959.42

Authors

sun, J.Q. (deposition date: 2024-01-21, release date: 2024-07-03, Last modification date: 2024-10-23)

Primary citation

Chen, J.,Sun, J.,Xu, Z.,Li, L.,Kang, X.,Luo, C.,Wang, Q.,Guo, X.,Li, Y.,Liu, K.,Wu, Y.
The binding and structural basis of fox ACE2 to RBDs from different sarbecoviruses.
Virol Sin, 39:609-618, 2024

PubMed Abstract: Foxes are susceptible to SARS-CoV-2 in laboratory settings, and there have also been reports of natural infections of both SARS-CoV and SARS-CoV-2 in foxes. In this study, we assessed the binding capacities of fox ACE2 to important sarbecoviruses, including SARS-CoV, SARS-CoV-2, and animal-origin SARS-CoV-2 related viruses. Our findings demonstrated that fox ACE2 exhibits broad binding capabilities to receptor-binding domains (RBDs) of sarbecoviruses. We further determined the cryo-EM structures of fox ACE2 complexed with RBDs of SARS-CoV, SARS-CoV-2 prototype (PT), and Omicron BF.7. Through structural analysis, we identified that the K417 mutation can weaken the ability of SARS-CoV-2 sub-variants to bind to fox ACE2, thereby reducing the susceptibility of foxes to SARS-CoV-2 sub-variants. In addition, the Y498 residue in the SARS-CoV RBD plays a crucial role in forming a vital cation-π interaction with K353 in the fox ACE2 receptor. This interaction is the primary determinant for the higher affinity of the SARS-CoV RBD compared to that of the SARS-CoV-2 PT RBD. These results indicate that foxes serve as potential hosts for numerous sarbecoviruses, highlighting the critical importance of surveillance efforts.

PubMed: 38866203
DOI: 10.1016/j.virs.2024.06.004

Experimental method

ELECTRON MICROSCOPY (3.12 Å)