8Z9I

Crystal structure of RaTG13 RBD bound to Rhinolophus affinis ACE2

Summary for 8Z9I

• Entry DOI: 10.2210/pdb8z9i/pdb
• Descriptor: RaTG13 Spike glycoprotein, Angiotensin-converting enzyme, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: ratg13 rbd, rhinolophus affinis ace2, viral protein-hydrolase complex, viral protein/hydrolase
• Biological source: Bat coronavirus RaTG13; More
• Total number of polymer chains: 4
• Total formula weight: 183710.40

Authors

Lan, J.,Wang, C.H. (deposition date: 2024-04-23, release date: 2025-04-30, Last modification date: 2025-05-14)

Primary citation

Wang, C.,Li, M.,Nan, X.,Deng, Y.,Fan, S.,Lan, J.
Molecular mechanisms of RaTG13 and SARS-CoV-2 RBD bound to Rhinolophus affinis bat ACE2.
Protein Sci., 34:e70117-e70117, 2025

PubMed Abstract: The discovery of the RaTG13 coronavirus in Rhinolophus affinis bats in 2013, sharing 96.3% genome homology with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), suggested bats as the origin of SARS-CoV-2. Although both human angiotensin-converting enzyme 2 (hACE2) and Rhinolophus affinis bat ACE2 (bACE2-Ra, seven polymorphic variants named 01-07) are known to serve as entry receptors for these coronaviruses, the binding mechanism of RaTG13 receptor binding domain (RBD) bound to bACE2-Ra remains poorly understood. Here, we found that RaTG13 RBD bound to bACE2-Ra-07 with a weaker affinity (2.42 μM) compared with SARS-CoV-2 RBD (372 nM). Additional glycosylation at residue N370 of RaTG13 had little influence on bACE2-Ra-07 binding by RaTG13 RBD. Crystal structures of the SARS-CoV-2 and RaTG13 N370Q RBD bound to bACE2-Ra-07 were solved. Interface analysis and surface plasmon resonance (SPR) assay indicated that residue substitutions at 493, 498, 501, and 505 may play a more important role in the cross-species recognition of bACE2-Ra-07 by the SARS-CoV-2 RBD. Besides, the N370Q mutation enhanced the binding affinity between the RBD of pangolin coronavirus isolated from Guangxi (PCoV-GX) and the bACE2-Ra-07 receptor by over 10-fold. Furthermore, the recently prevalent SARS-CoV-2 variant RBDs extensively retained the interaction with the bACE2-Ra-07 receptor. Our findings give new lights on the cross-species evolution of SARS-CoV-2 and prompt the urgency to monitor the circulation of coronaviruses in bats to better prevent future spillover.

PubMed: 40260962
DOI: 10.1002/pro.70117

Experimental method

X-RAY DIFFRACTION (3.011 Å)