7CDJ

Crystal structure of SARS-CoV-2 antibody P2C-1A3 with RBD

Summary for 7CDJ

• Entry DOI: 10.2210/pdb7cdj/pdb
• Descriptor: Spike protein S1, antibody P2C-1A3 heavy chain, antibody P2C-1A3 light chain, ... (4 entities in total)
• Functional Keywords: spike, receptor binding domain, antibody, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 3
• Total formula weight: 71259.63

Authors

Wang, X.,Zhang, L.,Ge, J.,Wang, R. (deposition date: 2020-06-19, release date: 2020-11-18, Last modification date: 2024-11-06)

Primary citation

Ge, J.,Wang, R.,Ju, B.,Zhang, Q.,Sun, J.,Chen, P.,Zhang, S.,Tian, Y.,Shan, S.,Cheng, L.,Zhou, B.,Song, S.,Zhao, J.,Wang, H.,Shi, X.,Ding, Q.,Liu, L.,Zhao, J.,Zhang, Z.,Wang, X.,Zhang, L.
Antibody neutralization of SARS-CoV-2 through ACE2 receptor mimicry.
Nat Commun, 12:250-250, 2021

PubMed Abstract: Understanding the mechanism for antibody neutralization of SARS-CoV-2 is critical for the development of effective therapeutics and vaccines. We recently isolated a large number of monoclonal antibodies from SARS-CoV-2 infected individuals. Here we select the top three most potent yet variable neutralizing antibodies for in-depth structural and functional analyses. Crystal structural comparisons reveal differences in the angles of approach to the receptor binding domain (RBD), the size of the buried surface areas, and the key binding residues on the RBD of the viral spike glycoprotein. One antibody, P2C-1F11, most closely mimics binding of receptor ACE2, displays the most potent neutralizing activity in vitro and conferred strong protection against SARS-CoV-2 infection in Ad5-hACE2-sensitized mice. It also occupies the largest binding surface and demonstrates the highest binding affinity to RBD. More interestingly, P2C-1F11 triggers rapid and extensive shedding of S1 from the cell-surface expressed spike glycoprotein, with only minimal such effect by the remaining two antibodies. These results offer a structural and functional basis for potent neutralization via disruption of the very first and critical steps for SARS-CoV-2 cell entry.

PubMed: 33431856
DOI: 10.1038/s41467-020-20501-9

Experimental method

X-RAY DIFFRACTION (3.396 Å)