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 spatial organizations of MERS-CoV and SARS-CoV S proteins resemble that of influenza virus hemagglutinin (HA) protein, which also has two cleaved subunits (HA1 and HA2) and the HA1 subunit must dissociate from HA2 before activation of membrane fusion under low pH environment in the endosome 21 . A feasible membrane fusion process of MERS-CoV and SARS-CoV is proposed bellow. Taking MERS-CoV as an example, the receptor binding to the RBD region may help to keep the RBD in the 'standing' state, which facilitates the dissociation of the S1 subunit from the S2 subunit. When the S1 subunit is dissociated from the S2 subunit (Fig. 6) , a second S2 0 cleavage can release the fusion peptide. The connecting region, HR1 region and central helix would form an extremely long helix (at least 200 Ã…) to insert the fusion peptide into the host cell membrane (Fig. 6) , which is deduced from the fusion process of the influenza HA protein. Finally, the HR1 and HR2 regions will form a coiled structure and assemble into a six-helix bundle to drag the viral and host membranes together (Fig. 6) .