Human coronavirus (CoV) HKU1 is a pathogen causing acute respiratory illnesses and so far little is known about its biology. HKU1 virus uses its S1 subunit C-terminal domain (CTD) and not the N-terminal domain like other lineage A β-CoVs to bind to its yet unknown human receptor. Here we present the crystal structure of HKU1 CTD at 1.9 Å resolution. The structure consists of three subdomains: core, insertion and subdomain-1 (SD-1). While the structure of the core and SD-1 subdomains of HKU1 are highly similar to those of other β-CoVs, the insertion subdomain adopts a novel fold, which is largely invisible in the cryo-EM structure of the HKU1 S trimer. We identify five residues in the insertion subdomain that are critical for binding of neutralizing antibodies and two residues essential for receptor binding. Our study contributes to a better understanding of entry, immunity and evolution of CoV S proteins. Human coronavirus HKU1 can cause severe respiratory diseases in young children and immunocompromised patients. Here, the authors present the structure of the C-terminal domain of the viral spike glycoprotein S1 subunit, which is important for host cell receptor binding.
【초록키워드】 neutralizing antibody, Evolution, coronavirus, Immunity, children, Human, Immunocompromised patients, virus, pathogen, Lineage, CoV, glycoprotein, receptor, Critical, HKU1, binding, N-terminal domain, C-terminal domain, S1 subunit, Receptor binding, severe respiratory disease, residue, S proteins, host cell receptor, insertion, viral spike, β-CoVs, while, β-CoV, FIVE, cryo-EM structure, S trimer, identify, contribute, CTD, acute respiratory illness, 【제목키워드】 spike glycoprotein, Receptor binding domain, crystal structure, HKU1, human betacoronavirus,