Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4 |
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Authors: | Nianshuang Wang Xuanling Shi Liwei Jiang Senyan Zhang Dongli Wang Pei Tong Dongxing Guo Lili Fu Ye Cui Xi Liu Kelly C Arledge Ying-Hua Chen Linqi Zhang Xinquan Wang |
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Affiliation: | 1.Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China;2.Comprehensive AIDS Research Center, Research Center for Public Health, School of Medicine, Tsinghua University, Beijing 100084, China |
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Abstract: | The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 Å-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 β-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection. |
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Keywords: | MERS-CoV DPP4 RBD viral infection complex structure |
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