Conformational change and protein-protein interactions of the fusion protein of Semliki Forest virus.
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.
Gibbons
Don L
DL
Virologie Moléculaire & Structurale, UMR 2472/1157 CNRS-INRA, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
Vaney
Marie-Christine
MC
Roussel
Alain
A
Vigouroux
Armelle
A
Reilly
Brigid
B
Lepault
Jean
J
Kielian
Margaret
M
Rey
Félix A
FA
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
D014760:Viral Fusion Proteins