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

作　　者：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 

机构地区：[1]Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua Uni-versity, Beo'ing 100084, China,' [2]Comprehensive AIDS Research Center, Research Center for Public Health, School of Medicine,Tsinghua University, Beijing 100084, China

出　　处：《Cell Research》2013年第8期986-993,共8页细胞研究（英文版）

摘　　要：The spike glycoprotein （S） of recently identified Middle East respiratory syndrome coronavirus （MERS-CoV） tar- gets 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 X- 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 IS-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.The spike glycoprotein （S） of recently identified Middle East respiratory syndrome coronavirus （MERS-CoV） tar- gets 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 X- 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 IS-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.

关 键 词：MERS-CoV DPP4 RBD viral infection complex structure 

分 类 号：Q26[生物学—细胞生物学] S852.65[农业科学—基础兽医学]