title: Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains.
abstract: The envelope spike (S) proteins of MERS-CoV and SARS-CoV determine the virus host tropism and entry into host cells, and constitute a promising target for the development of prophylactics and therapeutics. Here, we present high-resolution structures of the trimeric MERS-CoV and SARS-CoV S proteins in its pre-fusion conformation by single particle cryo-electron microscopy. The overall structures resemble that from other coronaviruses including HKU1, MHV and NL63 reported recently, with the exception of the receptor binding domain (RBD). We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor. Further sequence conservation analysis of six human-infecting coronaviruses revealed that the fusion peptide, HR1 region and the central helix are potential targets for eliciting broadly neutralizing antibodies.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Duanfang
authors.initials: D
authors.lastname: Cao
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Biotechnology, Tianjin 300308, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.affiliation: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Qihui
authors.initials: Q
authors.lastname: Wang
authors.affiliation: West China Hospital Emergency Department (WCHED), State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Guangwen
authors.initials: G
authors.lastname: Lu
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.|Center for Influenza Research and Early-warning, Chinese Academy of Sciences (CASCIRE), Beijing 100101, China.|Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.|Center for Influenza Research and Early-warning, Chinese Academy of Sciences (CASCIRE), Beijing 100101, China.|Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|Center for Biological Imaging, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xinzheng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Biotechnology, Tianjin 300308, China.|Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.|Center for Influenza Research and Early-warning, Chinese Academy of Sciences (CASCIRE), Beijing 100101, China.|Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.|National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D057134:Antibodies, Neutralizing; D000998:Antiviral Agents / Q000494:pharmacology; D020285:Cryoelectron Microscopy; D006023:Glycoproteins / Q000737:chemistry* / Q000648:ultrastructure*; D006031:Glycosylation; D008561:Membrane Fusion / Q000187:drug effects; D065207:Middle East Respiratory Syndrome Coronavirus / Q000648:ultrastructure*; D008958:Models, Molecular; D011485:Protein Binding; D000072417:Protein Domains; D055503:Protein Multimerization; D011991:Receptors, Virus / Q000378:metabolism*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000648:ultrastructure*; D064370:Spike Glycoprotein, Coronavirus / Q000737:chemistry / Q000648:ultrastructure
chemical_list: D057134:Antibodies, Neutralizing; D000998:Antiviral Agents; D006023:Glycoproteins; D011991:Receptors, Virus; D064370:Spike Glycoprotein, Coronavirus; C578557:spike glycoprotein, SARS-CoV