title: Structural basis for coronavirus-mediated membrane fusion. Crystal structure of mouse hepatitis virus spike protein fusion core.
abstract: The surface transmembrane glycoprotein is responsible for mediating virion attachment to cell and subsequent virus-cell membrane fusion. However, the molecular mechanisms for the viral entry of coronaviruses remain poorly understood. The crystal structure of the fusion core of mouse hepatitis virus S protein, which represents the first fusion core structure of any coronavirus, reveals a central hydrophobic coiled coil trimer surrounded by three helices in an oblique, antiparallel manner. This structure shares significant similarity with both the low pH-induced conformation of influenza hemagglutinin and fusion core of HIV gp41, indicating that the structure represents a fusion-active state formed after several conformational changes. Our results also indicate that the mechanisms for the viral fusion of coronaviruses are similar to those of influenza virus and HIV. The coiled coil structure has unique features, which are different from other viral fusion cores. Highly conserved heptad repeat 1 (HR1) and HR2 regions in coronavirus spike proteins indicate a similar three-dimensional structure among these fusion cores and common mechanisms for the viral fusion. We have proposed the binding regions of HR1 and HR2 of other coronaviruses and a structure model of their fusion core based on our mouse hepatitis virus fusion core structure and sequence alignment. Drug discovery strategies aimed at inhibiting viral entry by blocking hairpin formation may be applied to the inhibition of a number of emerging infectious diseases, including severe acute respiratory syndrome.
authors.affiliation: Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Xu
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lou
authors.forename: Lan
authors.initials: L
authors.lastname: Qin
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Bai
authors.forename: Hai
authors.initials: H
authors.lastname: Pang
authors.forename: Po
authors.initials: P
authors.lastname: Tien
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017934:Coronavirus / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019281:Dimerization; D004926:Escherichia coli / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D006517:Murine hepatitis virus / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000737:chemistry*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008562:Membrane Glycoproteins; D010455:Peptides; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus