期刊
CELL RESEARCH
卷 23, 期 8, 页码 986-993出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cr.2013.92
关键词
MERS-CoV; DPP4; RBD; viral infection; complex structure
类别
资金
- Ministry of Science and Technology [2010CB912402, 2011CB910502]
- Ministry of Health [2012ZX10001009]
- Fok Ying Tung Education Foundation
- National Outstanding Youth Award [30825035]
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 angstrom-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 beta-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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