Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains

Yuan, Yuan; Cao, Duanfang; Zhang, Yanfang; Ma, Jun; Qi, Jianxun; Wang, Qihui; Lu, Guangwen; Wu, Ying; Yan, Jinghua; Shi, Yi; Zhang, Xinzheng; Gao, George F.

To date, little is known about the structural and functional information of NTDs for the MERS-CoV or SARS-CoV S proteins, though its counterparts from other CoVs, such as mouse hepatitis virus (MHV) and bovine coronavirus (BCoV), act as receptor binding domains and their crystal structures have already been delineated. Our crystal and cryo-EM structures show that MERS-CoV and SARS-CoV NTDs fold into galectin-like structures as in BCoV, MHV and HKU1CoV (Supplementary Figs 9 and 10). However, the glycan-binding site on the top of MERS-CoV NTD is occupied by a short helix and the N-linked glycan on that helix, and thus NTD in this conformation maybe unable to attach the cell surface by recognizing certain sugar molecules, unlike BCoV and HKU1 (refs 25,26) . In addition to the NTD and RBD domains, the S1 subunits of both MERS-CoV and SARS-CoV contain two subdomains (I and II) that appear to be the base to underpin the NTD and RBD domains (Fig. 2) . These two subdomains are primarily composed of amino acids following the RBD domain, and the linker region between the NTD and RBD, as well as residues adjacent to the S2 cleavage site, also contribute to the formation of the subdomains.