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-Structure paper
タイトル | Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite. |
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ジャーナル・号・ページ | Cell Host Microbe, Vol. 29, Issue 5, Page 819-833.e7, Year 2021 |
掲載日 | 2021年5月12日 |
著者 | Gabriele Cerutti / Yicheng Guo / Tongqing Zhou / Jason Gorman / Myungjin Lee / Micah Rapp / Eswar R Reddem / Jian Yu / Fabiana Bahna / Jude Bimela / Yaoxing Huang / Phinikoula S Katsamba / Lihong Liu / Manoj S Nair / Reda Rawi / Adam S Olia / Pengfei Wang / Baoshan Zhang / Gwo-Yu Chuang / David D Ho / Zizhang Sheng / Peter D Kwong / Lawrence Shapiro / |
PubMed 要旨 | Numerous antibodies that neutralize SARS-CoV-2 have been identified, and these generally target either the receptor-binding domain (RBD) or the N-terminal domain (NTD) of the viral spike. While RBD- ...Numerous antibodies that neutralize SARS-CoV-2 have been identified, and these generally target either the receptor-binding domain (RBD) or the N-terminal domain (NTD) of the viral spike. While RBD-directed antibodies have been extensively studied, far less is known about NTD-directed antibodies. Here, we report cryo-EM and crystal structures for seven potent NTD-directed neutralizing antibodies in complex with spike or isolated NTD. These structures defined several antibody classes, with at least one observed in multiple convalescent donors. The structures revealed that all seven antibodies target a common surface, bordered by glycans N17, N74, N122, and N149. This site-formed primarily by a mobile β-hairpin and several flexible loops-was highly electropositive, located at the periphery of the spike, and the largest glycan-free surface of NTD facing away from the viral membrane. Thus, in contrast to neutralizing RBD-directed antibodies that recognize multiple non-overlapping epitopes, potent NTD-directed neutralizing antibodies appear to target a single supersite. |
リンク | Cell Host Microbe / PubMed:33789084 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.97 - 4.47 Å |
構造データ | EMDB-23125, PDB-7l2d: EMDB-23126, PDB-7l2e: EMDB-23127, PDB-7l2f: EMDB-23150: EMDB-23151: EMDB-23489, PDB-7lqv: EMDB-23490, PDB-7lqw: PDB-7l2c: |
化合物 | ChemComp-NAG: ChemComp-CA: ChemComp-ACT: ChemComp-CAC: ChemComp-PGE: ChemComp-HOH: |
由来 |
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キーワード | IMMUNE SYSTEM/Viral Protein (免疫系) / COVID-19 (新型コロナウイルス感染症 (2019年)) / SARS-CoV-2 (SARSコロナウイルス2) / Viral protein (ウイルスタンパク質) / Spike glycoprotein (スパイクタンパク質) / N-terminal domain (N末端) / NTD / Neutralizing antibody (中和抗体) / 2-51 / Fab / IMMUNE SYSTEM (免疫系) / IMMUNE SYSTEM-Viral Protein complex (免疫系) / Viral protein/Immune system (ウイルス性) / Fusion protein (融合タンパク質) / NTD-directed antibody / 1-87 / Viral protein-Immune system complex (ウイルス性) / 4-18 / 5-24 / COVID (新型コロナウイルス感染症 (2019年)) / COVID19 (新型コロナウイルス感染症 (2019年)) / SARS-CoV2 (SARSコロナウイルス2) / prefusion / neutralizing (中和抗体) |