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.

Dynamic RBD domains of both S trimers. Recently, three pioneering studies on cryo-EM structures of the S ectodomain from MHV and hCoVs HKU1 and NL63 have revealed a similar overall structural fold of the full-length S protein [27] [28] [29] . Both the MHV and HKU1 S ectodomain structures display a domain swapping organization of NTD and CTD in a woven appearance when viewed from the top of the S trimer. The CTD is located at the trimer apex close to the three-fold axis, whereas the NL63 S ectodomain structure shows a packed NTD and CTD organization ( Supplementary Fig. 11) . Unfortunately, these studies do not disclose how receptor binding occurs in SARS-CoV or MERS-CoV. The structural alignment of the SARS-CoV, MERS-CoV and NL63 CTD-receptor complexes with the S ectodomain structures reveals that the receptor binding surface of the CTD is buried in the S protein trimer (lying state) and is therefore incapable of making equivalent interactions without some initial breathing and transient conformational changes. However, our unprecedented observation of an inherently flexible RBD in both the MERS-CoV and SARS-CoV S trimers provides a plausible explanation for the receptor binding process for the two CoVs, as the receptor binding surface can be fully exposed in the standing state.