Structures of synthetic nanobody-SARS-CoV-2 receptor-binding domain complexes reveal distinct sites of interaction

被引:23
作者
Ahmad, Javeed [1 ]
Jiang, Jiansheng [1 ]
Boyd, Lisa F. [1 ]
Zeher, Allison [2 ]
Huang, Rick [2 ]
Xia, Di [2 ]
Natarajan, Kannan [1 ]
Margulies, David H. [1 ]
机构
[1] NIAID, Mol Biol Sect, Lab Immune Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[2] NCI, Lab Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
SARS-COV-2; NANOBODIES; ANTIBODIES; VARIANT; SYSTEM; ENTRY;
D O I
10.1016/j.jbc.2021.101202
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Combating the worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of new variants demands understanding of the structural basis of the interaction of antibodies with the SARS-CoV-2 receptor binding domain (RBD). Here, we report five X-ray crystal structures of sybodies (synthetic nanobodies) including those of binary and ternary complexes of Sb16-RBD, Sb45-RBD, Sb14-RBD-Sb68, and Sb45-RBD-Sb68, as well as unliganded Sb16. These structures reveal that Sb14, Sb16, and Sb45 bind the RBD at the angiotensin-converting enzyme 2 interface and that the Sb16 interaction is accompanied by a large conformational adjustment of complementarity-determining region 2. In contrast, Sb68 interacts at the periphery of the SARSCoV-2 RBD-angiotensin-converting enzyme 2 interface. We also determined cryo-EM structures of Sb45 bound to the SARS-CoV-2 spike protein. Superposition of the X-ray structures of sybodies onto the trimeric spike protein cryo-EM map indicates that some sybodies may bind in both "up" and "down" configurations, but others may not. Differences in sybody recognition of several recently identified RBD variants are explained by these structures.
引用
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页数:15
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