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.

For MERS-CoV S trimer, two classes were found with one or two of the three S1 RBDs in the S trimer in the 'standing' state. The reconstructed maps of these two conformations were refined to 4.1 and 4.2 Ã… resolutions without symmetry imposed, respectively ( Supplementary Fig. 5 ). Aside from the RBD, the rest of the S1/S2 protein remained the same as in the trimer. To improve the resolution in the rest of the protein, we combined the data from both classes and determined the structure of MERS-CoV S ectodomain trimer with three-fold symmetry imposed at a resolution of 3.7 Ã… ( Supplementary Fig. 5 , see Methods). We also solved the crystal structure of the RBD-preceding N terminal domain (NTD, residues 18-353) in the S1 subunit at a resolution of 1.5 Ã…. An atomic model of the cleaved MERS-CoV S1/S2 trimer was built de novo using the 3.7 Ã… map, except for the flexible regions of S1 CTD and part of S1 NTD, which were fitted by crystal structures. For SARS-CoV S trimer, the structures of the two conformations with none or one of the three S1 RBDs in the 'standing' state were determined to resolutions of 3.2 Ã… (three-fold symmetry) and 3.7 Ã… (no symmetry), respectively (Supplementary Fig. 6 ). We also solved the crystal structure of the NTD at a resolution of 2.2 Ã…. An atomic model of the uncleaved SARS-CoV S trimer was built de novo using the 3.2 Ã… map, except the flexible RBD and part of the S1 NTD which were from fitted crystal structures. The final model includes residues 18-1,104, with several breaks due to the poor densities. The atomic model was used to interpret the 3.7 Ã… map after being fitted into the map by domains.