7B0B

Fab HbnC3t1p1_C6 bound to SARS-CoV-2 RBD

7B0B の概要

• エントリーDOI: 10.2210/pdb7b0b/pdb
• 分子名称: IGK@ protein, Fab heavy chain, Surface glycoprotein, ... (4 entities in total)
• 機能のキーワード: sars-cov-2, neutralizing monoclonal antibody, receptor-binding motif, receptor-binding domain, antiviral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 74452.25

構造登録者

Borenstein-Katz, A.,Diskin, R. (登録日: 2020-11-19, 公開日: 2021-12-01, 最終更新日: 2024-10-16)

主引用文献

Korenkov, M.,Zehner, M.,Cohen-Dvashi, H.,Borenstein-Katz, A.,Kottege, L.,Janicki, H.,Vanshylla, K.,Weber, T.,Gruell, H.,Koch, M.,Diskin, R.,Kreer, C.,Klein, F.
Somatic hypermutation introduces bystander mutations that prepare SARS-CoV-2 antibodies for emerging variants.
Immunity, 56:2803-2815.e6, 2023

PubMed Abstract: Somatic hypermutation (SHM) drives affinity maturation and continues over months in SARS-CoV-2-neutralizing antibodies (nAbs). However, several potent SARS-CoV-2 antibodies carry no or only a few mutations, leaving the question of how ongoing SHM affects neutralization unclear. Here, we reverted variable region mutations of 92 antibodies and tested their impact on SARS-CoV-2 binding and neutralization. Reverting higher numbers of mutations correlated with decreasing antibody functionality. However, for some antibodies, including antibodies of the public clonotype VH1-58, neutralization of Wu01 remained unaffected. Although mutations were dispensable for Wu01-induced VH1-58 antibodies to neutralize Alpha, Beta, and Delta variants, they were critical for Omicron BA.1/BA.2 neutralization. We exploited this knowledge to convert the clinical antibody tixagevimab into a BA.1/BA.2 neutralizer. These findings broaden our understanding of SHM as a mechanism that not only improves antibody responses during affinity maturation but also contributes to antibody diversification, thus increasing the chances of neutralizing viral escape variants.

PubMed: 38035879
DOI: 10.1016/j.immuni.2023.11.004

実験手法

X-RAY DIFFRACTION (2.98 Å)