title: Structural basis for paramyxovirus-mediated membrane fusion.
abstract: Paramyxoviruses are responsible for significant human mortality and disease worldwide, but the molecular mechanisms underlying their entry into host cells remain poorly understood. We have solved the crystal structure of a fragment of the simian parainfluenza virus 5 fusion protein (SV5 F), revealing a 96 A long coiled coil surrounded by three antiparallel helices. This structure places the fusion and transmembrane anchor of SV5 F in close proximity with a large intervening domain at the opposite end of the coiled coil. Six amino acids, potentially part of the fusion peptide, form a segment of the central coiled coil, suggesting that this structure extends into the membrane. Deletion mutants of SV5 F indicate that putative flexible tethers between the coiled coil and the viral membrane are dispensable for fusion. The lack of flexible tethers may couple a final conformational change in the F protein directly to the fusion of two bilayers.
authors: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500, USA.
authors: K A
authors: KA
authors: Baker
authors: R E
authors: RE
authors: Dutch
authors: R A
authors: RA
authors: Lamb
authors: T S
authors: TS
authors: Jardetzky
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D003460:Crystallization; D019281:Dimerization; D004583:Electrons; D006860:Hydrogen Bonding; D007477:Ions; D008561:Membrane Fusion; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D018108:Respirovirus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D007477:Ions; D010446:Peptide Fragments; D014760:Viral Fusion Proteins