7XBG

The crystal structure of RshSTT182/200 RBD-insert2-T346R-Y496G mutant in complex with human ACE2

Summary for 7XBG

• Entry DOI: 10.2210/pdb7xbg/pdb
• Descriptor: Processed angiotensin-converting enzyme 2, RshSTT182/200 coronavirus receptor binding domain insert2 mutant, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: complex, viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 196074.23

Authors

Hu, Y.,Liu, K.F.,Han, P.,Qi, J.X. (deposition date: 2022-03-21, release date: 2023-01-11, Last modification date: 2024-11-06)

Primary citation

Hu, Y.,Liu, K.,Han, P.,Xu, Z.,Zheng, A.,Pan, X.,Jia, Y.,Su, C.,Tang, L.,Wu, L.,Bai, B.,Zhao, X.,Tian, D.,Chen, Z.,Qi, J.,Wang, Q.,Gao, G.F.
Host range and structural analysis of bat-origin RshSTT182/200 coronavirus binding to human ACE2 and its animal orthologs.
Embo J., 42:e111737-e111737, 2023

PubMed Abstract: Bat-origin RshSTT182 and RshSTT200 coronaviruses (CoV) from Rhinolophus shameli in Southeast Asia (Cambodia) share 92.6% whole-genome identity with SARS-CoV-2 and show identical receptor-binding domains (RBDs). In this study, we determined the structure of the RshSTT182/200 receptor binding domain (RBD) in complex with human angiotensin-converting enzyme 2 (hACE2) and identified the key residues that influence receptor binding. The binding of the RshSTT182/200 RBD to ACE2 orthologs from 39 animal species, including 18 bat species, was used to evaluate its host range. The RshSTT182/200 RBD broadly recognized 21 of 39 ACE2 orthologs, although its binding affinities for the orthologs were weaker than those of the RBD of SARS-CoV-2. Furthermore, RshSTT182 pseudovirus could utilize human, fox, and Rhinolophus affinis ACE2 receptors for cell entry. Moreover, we found that SARS-CoV-2 induces cross-neutralizing antibodies against RshSTT182 pseudovirus. Taken together, these findings indicate that RshSTT182/200 can potentially infect susceptible animals, but requires further evolution to obtain strong interspecies transmission abilities like SARS-CoV-2.

PubMed: 36519268
DOI: 10.15252/embj.2022111737

Experimental method

X-RAY DIFFRACTION (3.37 Å)