receptor-binding domain of the S1 subunit of the Spike (S) protein from human Middle East respiratory syndrome coronavirus
This group contains the receptor-binding domain (RBD) of the S1 subunit of the spike (S) protein from the human coronavirus that causes Middle East Respiratory Syndrome (MERS-CoV). MERS-CoV causes severe pulmonary disease in humans. The CoV S protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesized as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). While the RBD of mouse hepatitis virus (MHV) is located at the NTD, most CoVs, including MERS-CoV use the C-domain to bind their receptors. MERS-CoV use human dipeptidyl peptidase 4 (DPP4), also called CD26, as its receptor. It binds DPP4 through the RBD of its S1 subunit and then fuses viral and host membranes through its S2 subunit. Due to the key role of the S protein RBD in viral attachment, it is the major target for antibody-mediated neutralization. This model corresponds to the S1 subunit C-domain that serves as the RBD for most CoVs including MERS-CoV.
Comment:Human neutralizing antibodies recognize the receptor-binding domain of MERS-CoV S glycoprotein and interferes with the interaction between viral S and the human cellular receptor human dipeptidyl peptidase 4 (DPP4).
Structure:6NB3; MERS-CoV receptor-binding domain binds to human neutralizing LCA60 antibody, contacts at 4A
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