ジャーナル: Cell Rep / 年: 2021 タイトル: Modular basis for potent SARS-CoV-2 neutralization by a prevalent VH1-2-derived antibody class. 著者: Micah Rapp / Yicheng Guo / Eswar R Reddem / Jian Yu / Lihong Liu / Pengfei Wang / Gabriele Cerutti / Phinikoula Katsamba / Jude S Bimela / Fabiana A Bahna / Seetha M Mannepalli / Baoshan ...著者: Micah Rapp / Yicheng Guo / Eswar R Reddem / Jian Yu / Lihong Liu / Pengfei Wang / Gabriele Cerutti / Phinikoula Katsamba / Jude S Bimela / Fabiana A Bahna / Seetha M Mannepalli / Baoshan Zhang / Peter D Kwong / Yaoxing Huang / David D Ho / Lawrence Shapiro / Zizhang Sheng / 要旨: Antibodies with heavy chains that derive from the VH1-2 gene constitute some of the most potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies yet identified. To ...Antibodies with heavy chains that derive from the VH1-2 gene constitute some of the most potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies yet identified. To provide insight into whether these genetic similarities inform common modes of recognition, we determine the structures of the SARS-CoV-2 spike in complex with three VH1-2-derived antibodies: 2-15, 2-43, and H4. All three use VH1-2-encoded motifs to recognize the receptor-binding domain (RBD), with heavy-chain N53I-enhancing binding and light-chain tyrosines recognizing F486. Despite these similarities, class members bind both RBD-up and -down conformations of the spike, with a subset of antibodies using elongated CDRH3s to recognize glycan N343 on a neighboring RBD-a quaternary interaction accommodated by an increase in RBD separation of up to 12 Å. The VH1-2 antibody class, thus, uses modular recognition encoded by modular genetic elements to effect potent neutralization, with the VH-gene component specifying recognition of RBD and the CDRH3 component specifying quaternary interactions.