4L72

Crystal structure of MERS-CoV complexed with human DPP4

Summary for 4L72

• Entry DOI: 10.2210/pdb4l72/pdb
• Descriptor: Dipeptidyl peptidase 4, MERS-CoV RBD, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: alpha/beta hydrolase beta-propeller, glycolation, virus receptor-binding domain, hydrolase-viral protein complex, hydrolase/viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 109495.37

Authors

Wang, X.Q.,Wang, N.S. (deposition date: 2013-06-13, release date: 2013-08-21, Last modification date: 2024-11-13)

Primary citation

Wang, N.,Shi, X.,Jiang, L.,Zhang, S.,Wang, D.,Tong, P.,Guo, D.,Fu, L.,Cui, Y.,Liu, X.,Arledge, K.C.,Chen, Y.H.,Zhang, L.,Wang, X.
Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4
Cell Res., 23:986-993, 2013

PubMed 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.

PubMed: 23835475
DOI: 10.1038/cr.2013.92

Experimental method

X-RAY DIFFRACTION (3.005 Å)