Modular basis for potent SARS-CoV-2 neutralization by a prevalent VH1-2-derived antibody class.
Modular basis for potent SARS-CoV-2 neutralization by a prevalent VH1-2-derived antibody class.
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DOI：
10.1016/j.celrep.2021.108950
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发表时间：
2021-04-06
期刊：
影响因子：
8.8
通讯作者：
Sheng Z
中科院分区：
文献类型：
--
作者：
Rapp M;Guo Y;Reddem ER;Yu J;Liu L;Wang P;Cerutti G;Katsamba P;Bimela JS;Bahna FA;Mannepalli SM;Zhang B;Kwong PD;Huang Y;Ho DD;Shapiro L;Sheng Z
具有来自VH 1 -2基因的重链的抗体构成了一些最有效的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）中和抗体。为了深入了解这些遗传相似性是否为常见的识别模式提供信息，我们确定了SARS-CoV-2与三种VH 1 -2衍生抗体（2-15，2-43和H4）复合物的结构。所有三种都使用VH 1 -2编码的基序来识别受体结合结构域（RBD），重链N53 I增强结合，轻链酪氨酸识别F486 RBD。尽管存在这些相似性，但类成员结合刺突的RBD-向上和-向下构象，其中抗体的子集使用延长的CDRH 3来识别相邻RBD上的聚糖N343-通过RBD分离增加高达12 μ m的四级相互作用来调节。因此，VH 1 -2抗体类别使用由模块化遗传元件编码的模块化识别来实现有效的中和，其中VH-基因组分指定RBD的识别，并且CDRH 3组分指定四级相互作用。Rapp等人确定三种人源性VH 1 -2 SARS-CoV-2中和抗体的结构，并确定一种普遍的多供体抗体类别，其识别具有会聚重链和轻链模块的受体结合结构域（RBD）。它们进一步显示了RBD向上和RBD向下识别以及季铵化介导的尖峰构象变化的结构基础。
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 F486RBD. 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. Rapp et al. determine structures of three human VH1-2-derived SARS-CoV-2-neutralizing antibodies and define a prevalent multi-donor antibody class that recognizes the receptor-binding domain (RBD) with convergent heavy- and light-chain modules. They further show the structural basis for RBD-up and RBD-down recognition and quaternary recognition-mediated spike-conformation change.
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DOI：
10.1126/science.abg3055
发表时间：
2021-04-09
期刊：
Science (New York, N.Y.)
影响因子：
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DOI：
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发表时间：
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影响因子：
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