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-Structure paper
タイトル | Modular basis for potent SARS-CoV-2 neutralization by a prevalent VH1-2-derived antibody class. |
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ジャーナル・号・ページ | Cell Rep, Vol. 35, Issue 1, Page 108950, Year 2021 |
掲載日 | 2021年4月6日 |
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 / |
PubMed 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. |
リンク | Cell Rep / PubMed:33794145 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 3.18 - 5.87 Å |
構造データ | EMDB-23165, PDB-7l56: EMDB-23166, PDB-7l57: EMDB-23167, PDB-7l58: PDB-7l5b: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN/Immune System / SARS-CoV-2 / spike / glycoprotein / antibody / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex / Spike protein S1 / receptor binding protein SARS COV-2 |