8I5I

Crystal structure of SARS-CoV-2 delta variant spike receptor-binding domain (RBD) in complex with NCV2SG53 Fab

Summary for 8I5I

• Entry DOI: 10.2210/pdb8i5i/pdb
• Related: 7WN2 7WNB 7YOW 8I5H
• Descriptor: Spike protein S1, Fab Heavy chain, Fab Light chain (3 entities in total)
• Functional Keywords: spike, coronavirus, viral protein, fab, virus, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 3
• Total formula weight: 72693.51

Authors

Yamamoto, A.,Higashiura, A. (deposition date: 2023-01-25, release date: 2023-04-19, Last modification date: 2024-10-30)

Primary citation

Shitaoka, K.,Higashiura, A.,Kawano, Y.,Yamamoto, A.,Mizoguchi, Y.,Hashiguchi, T.,Nishimichi, N.,Huang, S.,Ito, A.,Ohki, S.,Kanda, M.,Taniguchi, T.,Yoshizato, R.,Azuma, H.,Kitajima, Y.,Yokosaki, Y.,Okada, S.,Sakaguchi, T.,Yasuda, T.
Structural basis of spike RBM-specific human antibodies counteracting broad SARS-CoV-2 variants.
Commun Biol, 6:395-395, 2023

PubMed Abstract: The decrease of antibody efficacy to mutated SARS-CoV-2 spike RBD explains the breakthrough infections and reinfections by Omicron variants. Here, we analyzed broadly neutralizing antibodies isolated from long-term hospitalized convalescent patients of early SARS-CoV-2 strains. One of the antibodies named NCV2SG48 is highly potent to broad SARS-CoV-2 variants including Omicron BA.1, BA.2, and BA.4/5. To reveal the mode of action, we determined the sequence and crystal structure of the Fab fragment of NCV2SG48 in a complex with spike RBD from the original, Delta, and Omicron BA.1. NCV2SG48 is from a minor V but the multiple somatic hypermutations contribute to a markedly extended binding interface and hydrogen bonds to interact with conserved residues at the core receptor-binding motif of RBD, which efficiently neutralizes a broad spectrum of variants. Thus, eliciting the RBD-specific B cells to the longitudinal germinal center reaction confers potent immunity to broad SARS-CoV-2 variants emerging one after another.

PubMed: 37041231
DOI: 10.1038/s42003-023-04782-6

Experimental method

X-RAY DIFFRACTION (3.06 Å)