8K4U

Structure of BtKY72 spike receptor-binding domain (RBD) complexed with bat ACE2

Summary for 8K4U

• Entry DOI: 10.2210/pdb8k4u/pdb
• EMDB information: 36892
• Descriptor: BtKY72, ACE2, ZINC ION (3 entities in total)
• Functional Keywords: btky72 rbd ace2 bat, viral protein
• Biological source: Severe acute respiratory syndrome-related coronavirus; More
• Total number of polymer chains: 2
• Total formula weight: 95023.27

Authors

Su, C.,Qi, J.X.,Gao, G.F. (deposition date: 2023-07-20, release date: 2024-06-19, Last modification date: 2025-07-02)

Primary citation

Su, C.,He, J.,Wang, L.,Hu, Y.,Cao, J.,Bai, B.,Qi, J.,Gao, G.F.,Yang, M.,Wang, Q.
Structural characteristics of BtKY72 RBD bound to bat ACE2 reveal multiple key residues affecting ACE2 usage of sarbecoviruses.
Mbio, 15:e0140424-e0140424, 2024

PubMed Abstract: Two different sarbecoviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2, have caused serious challenges to public health. Certain sarbecoviruses utilize angiotensin-converting enzyme 2 (ACE2) as their cellular receptor, whereas some do not, speculatively due to the two deletions in their receptor-binding domain (RBD). However, it remains unclear whether sarbecoviruses with one deletion in the RBD can still bind to ACE2. Here, we showed that two phylogenetically related sarbecoviruses with one deletion, BtKY72 and BM48-31, displayed a different ACE2-usage range. The cryo-electron microscopy structure of BtKY72 RBD bound to bat ACE2 identified a key residue important for the interaction between RBD and ACE2. In addition, we demonstrated that the mutations involving four types of core residues enabled the sarbecoviruses with deletion(s) to bind to human ACE2 (hACE2) and broadened the ACE2 usage of SARS-CoV-2. Our findings help predict the potential hACE2-binding ability to emerge sarbecoviruses and develop pan-sarbecovirus therapeutic agents.

PubMed: 39082798
DOI: 10.1128/mbio.01404-24

Experimental method

ELECTRON MICROSCOPY (3.2 Å)