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.

The MERS-CoV S1/S2 trimers could be classified into two classes with one (40% of particles) or two (60% of particles) RBDs in the standing state, and we cannot detect other conformations with all three RBDs in the standing or lying state. However, disassociated MERS-CoV S1 trimer particles were easily recognized during two-dimensional (2D) classification, which is consistent with the gel filtration result of the cleaved S protein as described above. We then reconstructed the cryo-EM structure of the disassociated MERS-CoV S1 trimer at a resolution of 9.5 Ã… (Fig. 3a, Supplementary Fig. 12 ). The disassociated S1 trimer forms a ring like structure, including the NTD domain, RBD domain and subdomains 1 and 2 (Fig. 3b) . All three RBD domains are in a standing conformation (Fig. 3b) . It implicates that the S1 trimer with three standing RBD domains is easily disassociated from the S2 moiety, and thus the stable S trimer particles with three standing RBD domains was rarely observed. Further analysis showed that the S1 trimer is stabilized by the interaction between the RBD core subdomain, subdomain 1 of one S1 protomer and the NTD domain of the neighbouring S1 protomer (Fig. 3c,d) .