title: Structures and polymorphic interactions of two heptad-repeat regions of the SARS virus S2 protein.
abstract: Entry of SARS coronavirus into its target cell requires large-scale structural transitions in the viral spike (S) glycoprotein in order to induce fusion of the virus and cell membranes. Here we describe the identification and crystal structures of four distinct alpha-helical domains derived from the highly conserved heptad-repeat (HR) regions of the S2 fusion subunit. The four domains are an antiparallel four-stranded coiled coil, a parallel trimeric coiled coil, a four-helix bundle, and a six-helix bundle that is likely the final fusogenic form of the protein. When considered together, the structural and thermodynamic features of the four domains suggest a possible mechanism whereby the HR regions, initially sequestered in the native S glycoprotein spike, are released and refold sequentially to promote membrane fusion. Our results provide a structural framework for understanding the control of membrane fusion and should guide efforts to intervene in the SARS coronavirus entry process.
authors.affiliation: Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Deng
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.forename: Wei
authors.initials: W
authors.lastname: Yong
authors.forename: Min
authors.initials: M
authors.lastname: Lu
mesh_terms: D018360:Crystallography, X-Ray; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid; D064370:Spike Glycoprotein, Coronavirus; D013816:Thermodynamics; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV