title: Solution structure of the severe acute respiratory syndrome-coronavirus heptad repeat 2 domain in the prefusion state.
abstract: The envelope glycoprotein, termed the spike protein, of severe acute respiratory syndrome coronavirus (SARS-CoV) is known to mediate viral entry. Similar to other class 1 viral fusion proteins, the heptad repeat regions of SARS-CoV spike are thought to undergo conformational changes from a prefusion form to a subsequent post-fusion form that enables fusion of the viral and host membranes. Recently, the structure of a post-fusion form of SARS-CoV spike, which consists of isolated domains of heptad repeats 1 and 2 (HR1 and HR2), has been determined by x-ray crystallography. To date there is no structural information for the prefusion conformations of SARS-CoV HR1 and HR2. In this work we present the NMR structure of the HR2 domain (residues 1141-1193) from SARS-CoV (termed S2-HR2) in the presence of the co-solvent trifluoroethanol. We find that in the absence of HR1, S2-HR2 forms a coiled coil symmetric trimer with a complex molecular mass of 18 kDa. The S2-HR2 structure, which is the first example of the prefusion form of coronavirus envelope, supports the current model of viral membrane fusion and gives insight into the design of structure-based antagonists of SARS.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
authors.forename: Susanna
authors.initials: S
authors.lastname: Hakansson-McReynolds
authors.forename: Shaokai
authors.initials: S
authors.lastname: Jiang
authors.forename: Lijun
authors.initials: L
authors.lastname: Rong
authors.forename: Michael
authors.initials: M
authors.lastname: Caffrey
mesh_terms: D018360:Crystallography, X-Ray; D006389:Hemagglutinins, Viral; D006801:Humans; D008562:Membrane Glycoproteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000138:chemical synthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D006389:Hemagglutinins, Viral; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins