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

By Nianshuang Wang, Xuanling Shi, Liwei Jiang, Senyan Zhang, Dongli Wang, Pei Tong, D. Guo, L. Fu, Ye Cui, Xi Liu and 4 more. Cell Research, 2013

730 citations recorded by the source corpus.

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.

Subfields: Animal Science and Zoology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/18d7f4c8e204349b39a037c19874cff1b34d0f97

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In Animal Science and Zoology

1. A. Tortoricia
2. M. A. Tortorici
3. David Veeslera
4. Fang Li

In Infectious Diseases

1. A. Tortoricia
2. M. A. Tortorici
3. David Veeslera
4. Abdo A. Elfiky
5. Fang Li
6. F. Krammer
7. D. Veesler

Citations in the corpus

• Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus (2015, neutral): “The experimental structure of MERS-CoV RBD was available (10, 11), whereas the structure of LCA60 was predicted by homology modeling according to the canonical structure method (15).”
• COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses (2020, neutral): “MERS-coronavirus employs dipeptidyl peptidase 4 (DPP4), while HCoV-NL63 and SARS-coronavirus require angiotensin-converting enzyme 2 (ACE2) as a key receptor [2,26].”
• Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen (2017, background): “However, the S protein ectodomain from MERS-CoV is less stable and more difficult to produce than other S proteins, and soluble constructs of the RBD have been the main focus of structural studies (14, 16), antibody isolation efforts (21, 23–25), and subunit vaccine development (26).”
• Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains (2017, neutral): “In the S1 subunit, the receptor binding domain (RBD, also called the C terminal domain, CTD) is localized in the C-terminal region, spanning B 200 amino acids, and structural studies have revealed that the RBD consists of two subdomains: the core and external subdomains 14–17 .”
• Structural insights into coronavirus entry (2019, background): “2) (Li et al., 2005a; Lu et al., 2013; Wang et al., 2013; Wong et al., 2017; Wu et al., 2009) .”
• Crystal structure of the receptor binding domain of the spike glycoprotein of human betacoronavirus HKU1 (2017, background): “In contrast, most CoVs from lineage A b-CoVs, including mouse hepatitis virus (MHV), human CoV OC43 and bovine coronavirus (BCoV), use their NTDs to bind either receptor protein or sialic acid 17, 28 .”
• From SARS to MERS, Thrusting Coronaviruses into the Spotlight (2019, background): “The RBM comprises a four-stranded antiparallel β-sheet for connecting to the core via loops [57,62].”
• Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein (2017, positive): “The high sequence identity of spikeinteracting residues on dromedary and human DPP4 facilitates cross-species transmission without the need for adaptive mutations (17, 67).”
• CoV-AbDab: the Coronavirus Antibody Database (2020, background): “The spike (S) protein is known to mediate coronaviral entry into cells through a biochemical signal initiated by RBD-ACE2 (SARS-CoV) or RBD-DPP4 (MERS-CoV) binding (65, 71).”