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" Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein. "
Zhang, Senyan; Zhou, Panpan; Wang, Pengfei; Li, Yangyang; Jiang, Liwei; Jia, Wenxu; Wang, Han; Fan, Angela; Wang, Dongli; Shi, Xuanling; Fang, Xianyang; Hammel, Michal; Wang, Shuying; Wang, Xinquan; Zhang, Linqi
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AL
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| Record Number
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912235
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LA4gk9c5cv
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| Title & Author
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Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein. [Article]\ Zhang, Senyan; Zhou, Panpan; Wang, Pengfei; Li, Yangyang; Jiang, Liwei; Jia, Wenxu; Wang, Han; Fan, Angela; Wang, Dongli; Shi, Xuanling; Fang, Xianyang; Hammel, Michal; Wang, Shuying; Wang, Xinquan; Zhang, Linqi
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2018
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| Title of Periodical
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Lawrence Berkeley National Laboratory
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| Abstract
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The major mechanism of antibody-mediated neutralization of the Middle East respiratory syndrome coronavirus (MERS-CoV) involves competition with the cellular receptor dipeptidyl peptidase 4 (DPP4) for binding to the receptor-binding domain (RBD) of the spike (S) glycoprotein. Here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody MERS-4. Structurally, MERS-4 approached the RBD from the outside of the RBD-DPP4 binding interface. Such binding resulted in the folding of the β5-β6 loop toward a shallow groove on the RBD interface critical for accommodating DPP4. The key residues for binding are identified through site-directed mutagenesis. Structural modeling revealed that MERS-4 binds to RBD only in the "up" position in the S trimer. Furthermore, MERS-4 demonstrated synergy with several reported antibodies. These results indicate that MERS-4 neutralizes MERS-CoV by indirect rather than direct competition with DPP4. This mechanism provides a valuable addition for the combined use of antibodies against MERS-CoV infection.
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