7YTN

Crystal structure of SARS-CoV-2 Alpha RBD in complex with the D27LEY neutralizing antibody Fab fragment

Summary for 7YTN

• Entry DOI: 10.2210/pdb7ytn/pdb
• Descriptor: Heavy chain of Fab, Light chain of Fab, Spike protein S1 (3 entities in total)
• Functional Keywords: antibody, antigen, complex, sars-cov-2, rbd, antiviral protein, antiviral protein-viral protein complex, antiviral protein/viral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 80898.71

Authors

Jeong, B.S.,Jeon, J.Y.,Oh, B.H. (deposition date: 2022-08-15, release date: 2023-06-28, Last modification date: 2024-10-30)

Primary citation

Jeong, B.S.,Jeon, J.Y.,Lai, C.J.,Yun, H.Y.,Jung, J.U.,Oh, B.H.
Structural basis for the broad and potent cross-reactivity of an N501Y-centric antibody against sarbecoviruses.
Front Immunol, 13:1049867-1049867, 2022

PubMed Abstract: More than 80% of SARS-CoV-2 variants, including Alpha and Omicron, contain an N501Y mutation in the receptor-binding domain (RBD) of the spike protein. The N501Y change is an adaptive mutation enabling tighter interaction with the human ACE2 receptor. We have developed a broadly neutralizing antibody (nAb), D27LEY, whose binding affinity was intentionally optimized for Y501. This N501Y-centric antibody not only interacts with the Y501-containing RBDs of SARS-CoV-2 variants, including Omicron, with pico- or subnanomolar binding affinity, but also binds tightly to the RBDs with a different amino acid at residue 501. The crystal structure of the Fab fragment of D27LEY bound to the RBD of the Alpha variant reveals that the Y501-containing loop adopts a ribbon-like topology and serves as a small but major epitope in which Y501 is a part of extensive intermolecular interactions. A hydrophobic cleft on the most conserved surface of the RBD core serves as another major binding epitope. These data explain the broad and potent cross-reactivity of this N501Y-centric antibody, and suggest that a vaccine antigenic component composed of the RBD core and a part of receptor-binding motif (RBM) containing tyrosine at residue 501 might elicit broad and potent humoral responses across sarbecoviruses.

PubMed: 36466915
DOI: 10.3389/fimmu.2022.1049867

Experimental method

X-RAY DIFFRACTION (3.51 Å)