Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26

By Guangwen Lu, Yawei Hu, Qihui Wang, Jianxun Qi, F. Gao, Yan Li, Yanfang Zhang, Wei Zhang, Yuan Yuan, Jinku Bao and 4 more. Nature, 2013

721 citations recorded by the source corpus.

The newly emergent Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe pulmonary disease in humans, representing the second example of a highly pathogenic coronavirus, the first being SARS-CoV. CD26 (also known as dipeptidyl peptidase 4, DPP4) was recently identified as the cellular receptor for MERS-CoV. The engagement of the MERS-CoV spike protein with CD26 mediates viral attachment to host cells and virus–cell fusion, thereby initiating infection. Here we delineate the molecular basis of this specific interaction by presenting the first crystal structures of both the free receptor binding domain (RBD) of the MERS-CoV spike protein and its complex with CD26. Furthermore, binding between the RBD and CD26 is measured using real-time surface plasmon resonance with a dissociation constant of 16.7 nM. The viral RBD is composed of a core subdomain homologous to that of the SARS-CoV spike protein, and a unique strand-dominated external receptor binding motif that recognizes blades IV and V of the CD26 β-propeller. The atomic details at the interface between the two binding entities reveal a surprising protein–protein contact mediated mainly by hydrophilic residues. Sequence alignment indicates, among betacoronaviruses, a possible structural conservation for the region homologous to the MERS-CoV RBD core, but a high variation in the external receptor binding motif region for virus-specific pathogenesis such as receptor recognition.

Subfields: Cellular and Molecular Neuroscience, Microbiology, Oncology

View Paper: https://www.semanticscholar.org/paper/6acd0f0e3d77ac12a300815badb1c7126d45200c

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Citations in the corpus

• Middle East Respiratory Syndrome Coronavirus: Another Zoonotic Betacoronavirus Causing SARS-Like Disease (2015, background): “The host range is determined mainly by the binding of the MERS-CoV S protein to the host receptor DPP4, which is relatively conserved among mammalian species (30, 48, 49, 119, 120).”
• Identification of the Receptor-Binding Domain of the Spike Glycoprotein of Human Betacoronavirus HKU1 (2015, background): “Of note, the receptor binding motifs of many viral 486 spike proteins are comprised of residues that are spatial close but largely separated in 487 primary sequence (20, 21).”
• Repurposing of Clinically Developed Drugs for Treatment of Middle East Respiratory Syndrome Coronavirus Infection (2014, background): “identified as the functional cellular receptor for MERS-CoV (4, 5).”
• A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS (2020, positive): “In view of the ongoing COVID-19 pandemic and frequent MERS outbreaks, we sought to further develop vaccines against these two CoVs for pilot scale production in GMP grade manufacturing.”
• Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus (2017, methodology): “The crystal structure demonstrating the interactions between DPP4 and MERS spike binding domain has previously been reported (28), and the crystal structure is PDB ID 4KR0.”
• Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2 (2020, positive): “In light of the determinant role of SARS-RBD and MERS-RBD in receptor recognition (Li et al., 2003, 2005; Lu et al., 2013; Raj et al., 2013), the majority of neutralizing antibodies have been shown to target the RBD, exerting neutralization activity by disrupting virus/receptor engagement (Du et al.”
• 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): “The insertion loops of SARS-CoV and MERS-CoV contain the receptor-binding motifs essential for receptor interaction [25] [26] [27] .”
• 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).”