Volume 23, No 8, Aug 2013

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 23 Issue 8, August 2013: 986-993

ORIGINAL ARTICLES

Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4 

Nianshuang Wang^1,*, Xuanling Shi^2,*, Liwei Jiang², Senyan Zhang¹, Dongli Wang¹, Pei Tong¹, Dongxing Guo², Lili Fu², Ye Cui¹, Xi Liu¹, Kelly C Arledge², Ying-Hua Chen¹, Linqi Zhang² and Xinquan Wang¹

¹Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
²Comprehensive AIDS Research Center, Research Center for Public Health, School of Medicine, Tsinghua University, Beijing 100084, China Correspondence: Correspondence: Xinquan Wang, E-mail: xinquanwang@mail.tsinghua.edu.cn; Linqi Zhang, E-mail: zhanglinqi@tsinghua.edu.cn*These two authors contributed equally to this work.

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.

10.1038/cr.2013.92

FULL TEXT | PDF

Browse 2496