title: Conformational change and protein-protein interactions of the fusion protein of Semliki Forest virus.
abstract: Fusion of biological membranes is mediated by specific lipid-interacting proteins that induce the formation and expansion of an initial fusion pore. Here we report the crystal structure of the ectodomain of the Semliki Forest virus fusion glycoprotein E1 in its low-pH-induced trimeric form. E1 adopts a folded-back conformation that, in the final post-fusion form of the full-length protein, would bring the fusion peptide loop and the transmembrane anchor to the same end of a stable protein rod. The observed conformation of the fusion peptide loop is compatible with interactions only with the outer leaflet of the lipid bilayer. Crystal contacts between fusion peptide loops of adjacent E1 trimers, together with electron microscopy observations, suggest that in an early step of membrane fusion, an intermediate assembly of five trimers creates two opposing nipple-like deformations in the viral and target membranes, leading to formation of the fusion pore.
authors.affiliation: Virologie Moléculaire & Structurale, UMR 2472/1157 CNRS-INRA, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Don L
authors.initials: DL
authors.lastname: Gibbons
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Vaney
authors.forename: Alain
authors.initials: A
authors.lastname: Roussel
authors.forename: Armelle
authors.initials: A
authors.lastname: Vigouroux
authors.forename: Brigid
authors.initials: B
authors.lastname: Reilly
authors.forename: Jean
authors.initials: J
authors.lastname: Lepault
authors.forename: Margaret
authors.initials: M
authors.lastname: Kielian
authors.forename: Félix A
authors.initials: FA
authors.lastname: Rey
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012672:Semliki forest virus / Q000737:chemistry* / Q000648:ultrastructure; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D014760:Viral Fusion Proteins