6XC4

Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibody CC12.3

Summary for 6XC4

• Entry DOI: 10.2210/pdb6xc4/pdb
• Related: 6XC2 6XC3
• Descriptor: Spike protein S1, CC12.3 heavy chain, CC12.3 light chain, ... (5 entities in total)
• Functional Keywords: antibody, sars-cov-2, coronavirus, spike, immune system, immune system-viral protein complex, immune system/viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 6
• Total formula weight: 146251.34

Authors

Yuan, M.,Liu, H.,Wu, N.C.,Zhu, X.,Wilson, I.A. (deposition date: 2020-06-08, release date: 2020-07-08, Last modification date: 2024-10-23)

Primary citation

Yuan, M.,Liu, H.,Wu, N.C.,Lee, C.D.,Zhu, X.,Zhao, F.,Huang, D.,Yu, W.,Hua, Y.,Tien, H.,Rogers, T.F.,Landais, E.,Sok, D.,Jardine, J.G.,Burton, D.R.,Wilson, I.A.
Structural basis of a shared antibody response to SARS-CoV-2.
Science, 369:1119-1123, 2020

PubMed Abstract: Molecular understanding of neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could accelerate vaccine design and drug discovery. We analyzed 294 anti-SARS-CoV-2 antibodies and found that immunoglobulin G heavy-chain variable region 3-53 (IGHV3-53) is the most frequently used IGHV gene for targeting the receptor-binding domain (RBD) of the spike protein. Co-crystal structures of two IGHV3-53-neutralizing antibodies with RBD, with or without Fab CR3022, at 2.33- to 3.20-angstrom resolution revealed that the germline-encoded residues dominate recognition of the angiotensin I converting enzyme 2 (ACE2)-binding site. This binding mode limits the IGHV3-53 antibodies to short complementarity-determining region H3 loops but accommodates light-chain diversity. These IGHV3-53 antibodies show minimal affinity maturation and high potency, which is promising for vaccine design. Knowledge of these structural motifs and binding mode should facilitate the design of antigens that elicit this type of neutralizing response.

PubMed: 32661058
DOI: 10.1126/science.abd2321

Experimental method

X-RAY DIFFRACTION (2.341 Å)