Structural basis of a shared antibody response to SARS-CoV-2
Structural basis of a shared antibody response to SARS-CoV-2
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DOI：
10.1126/science.abd2321
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发表时间：
2020-08-28
期刊：
影响因子：
56.9
通讯作者：
Wilson, Ian A.
中科院分区：
文献类型：
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作者：
Yuan, Meng;Liu, Hejun;Wilson, Ian A.
对严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）中和抗体反应的分子理解可以加速疫苗设计和药物发现。我们分析了294个抗SARS-CoV-2抗体，发现免疫球蛋白G重链可变区3-53（IGHV 3 -53）是最常用的IGHV基因，用于靶向刺突蛋白的受体结合结构域（RBD）。在233- 3.20埃分辨率下，两种IGHV 3 -53-中和抗体与RBD（有或没有Fab CR 3022）的共晶体结构显示，种系编码的残基主导血管紧张素I转化酶2（ACE 2）结合位点的识别。这种结合模式将IGHV 3 -53抗体限制于短互补决定区H3环，但适应轻链多样性。这些IGHV 3 -53抗体显示最小的亲和力成熟和高效力，这对于疫苗设计是有希望的。这些结构基序和结合模式的知识应有助于设计抗原，引发这种类型的中和反应。
Molecular understanding of neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could accelerate vaccine design and drug discovery. We analyzed 294 anti-SARS-CoV-2 antibodies and found that immunoglobulin G heavy-chain variable region 3-53 (IGHV3-53) is the most frequently used IGHV gene for targeting the receptor-binding domain (RBD) of the spike protein. Co-crystal structures of two IGHV3-53-neutralizing antibodies with RBD, with or without Fab CR3022, at 233- to 3.20 -angstrom resolution revealed that the germline-encoded residues dominate recognition of the angiotensin I converting enzyme 2 (ACE2)-binding site. This binding mode limits the IGHV3-53 antibodies to short complementarity-determining region H3 loops but accommodates light-chain diversity. These IGHV3-53 antibodies show minimal affinity maturation and high potency, which is promising for vaccine design. Knowledge of these structural motifs and binding mode should facilitate the design of antigens that elicit this type of neutralizing response.