Crystal structure of the receptor binding domain of the spike glycoprotein of human betacoronavirus HKU1

By Xiuyuan Ou, Hongxin Guan, B. Qin, Z. Mu, J. Wojdyla, Meitian Wang, S. Dominguez, Zhaohui Qian, S. Cui. 2017

73 citations recorded by the source corpus.

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.

Subfields: Animal Science and Zoology, Infectious Diseases

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Citations in the corpus

Human coronaviruses OC43 and HKU1 bind to 9-O-acetylated sialic acids via a conserved receptor-binding site in spike protein domain A (2019, background): “According to recent publications, the RBS would not be in S1, but in a downstream domain (31, 32), the main argument being that HKU1 S1 does not detectably bind to glycoconjugates (30).”
Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag (2020, background): “The insert 4 is at the junction of the SD1 (sub domain 1) and SD2 (sub domain 2) of the S1 subunit (Ou et al., 2017).”