7XB1

Crystal structure of Omicron BA.3 RBD complexed with hACE2

Summary for 7XB1

• Entry DOI: 10.2210/pdb7xb1/pdb
• Descriptor: Angiotensin-converting enzyme 2, Spike protein S1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: sars-cov-2, omicron, rbd, hace2, complex structure, viral protein, hydrolase-viral protein complex, hydrolase/viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 93681.27

Authors

Li, W.,Meng, Y.,Liao, H. (deposition date: 2022-03-19, release date: 2022-07-06, Last modification date: 2024-10-23)

Primary citation

Li, L.,Liao, H.,Meng, Y.,Li, W.,Han, P.,Liu, K.,Wang, Q.,Li, D.,Zhang, Y.,Wang, L.,Fan, Z.,Zhang, Y.,Wang, Q.,Zhao, X.,Sun, Y.,Huang, N.,Qi, J.,Gao, G.F.
Structural basis of human ACE2 higher binding affinity to currently circulating Omicron SARS-CoV-2 sub-variants BA.2 and BA.1.1.
Cell, 185:2952-2960.e10, 2022

PubMed Abstract: The currently circulating Omicron sub-variants are the SARS-CoV-2 strains with the highest number of known mutations. Herein, we found that human angiotensin-converting enzyme 2 (hACE2) binding affinity to the receptor-binding domains (RBDs) of the four early Omicron sub-variants (BA.1, BA.1.1, BA.2, and BA.3) follows the order BA.1.1 > BA.2 > BA.3 ≈ BA.1. The complex structures of hACE2 with RBDs of BA.1.1, BA.2, and BA.3 reveal that the higher hACE2 binding affinity of BA.2 than BA.1 is related to the absence of the G496S mutation in BA.2. The R346K mutation in BA.1.1 majorly affects the interaction network in the BA.1.1 RBD/hACE2 interface through long-range alterations and contributes to the higher hACE2 affinity of the BA.1.1 RBD than the BA.1 RBD. These results reveal the structural basis for the distinct hACE2 binding patterns among BA.1.1, BA.2, and BA.3 RBDs.

PubMed: 35809570
DOI: 10.1016/j.cell.2022.06.023

Experimental method

X-RAY DIFFRACTION (2.7 Å)