title: Structural basis of eukaryotic cell-cell fusion.
abstract: Cell-cell fusion proteins are essential in development. Here we show that the C. elegans cell-cell fusion protein EFF-1 is structurally homologous to viral class II fusion proteins. The 2.6 Å crystal structure of the EFF-1 trimer displays the same 3D fold and quaternary conformation of postfusion class II viral fusion proteins, although it lacks a nonpolar "fusion loop," indicating that it does not insert into the target membrane. EFF-1 was previously shown to be required in both cells for fusion, and we show that blocking EFF-1 trimerization blocks the fusion reaction. Together, these data suggest that whereas membrane fusion driven by viral proteins entails leveraging of a nonpolar loop, EFF-1-driven fusion of cells entails trans-trimerization such that transmembrane segments anchored in the two opposing membranes are brought into contact at the tip of the EFF-1 trimer to then, analogous to SNARE-mediated vesicle fusion, zip the two membranes into one.
authors.affiliation: Institut Pasteur, Unité de Virologie Structurale, 25-28 Rue du Docteur Roux, 75724 Paris Cedex 15, France; CNRS UMR 3569, 25-28 Rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: Jimena
authors.initials: J
authors.lastname: Pérez-Vargas
authors.affiliation: Institut Pasteur, Unité de Virologie Structurale, 25-28 Rue du Docteur Roux, 75724 Paris Cedex 15, France; CNRS UMR 3569, 25-28 Rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krey
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Clari
authors.initials: C
authors.lastname: Valansi
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Ori
authors.initials: O
authors.lastname: Avinoam
authors.affiliation: Institut Pasteur, Protéopôle-Plate-forme de Cristallogenèse, CNRS UMR 3528, 25-28 Rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Haouz
authors.affiliation: Université Grenoble Alpes, 6 rue Jules Horowitz, UVHCI, 38042 Grenoble Cedex 9, France; CNRS, UVHCI, 6 rue Jules Horowitz, 38042 Grenoble Cedex 9, France; Unit for Virus Host-Cell Interactions, 6 rue Jules Horowitz, Université Grenoble Alpes-EMBL-CNRS, 38042 Grenoble Cedex 9, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Jamin
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Raveh-Barak
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel. Electronic address: podbilew@technion.ac.il.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Podbilewicz
authors.affiliation: Institut Pasteur, Unité de Virologie Structurale, 25-28 Rue du Docteur Roux, 75724 Paris Cedex 15, France; CNRS UMR 3569, 25-28 Rue du Docteur Roux, 75724 Paris Cedex 15, France. Electronic address: rey@pasteur.fr.
authors.forename: Félix A
authors.initials: FA
authors.lastname: Rey
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002459:Cell Fusion; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D015726:Giant Cells / Q000378:metabolism; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D058105:Polymerization; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C470734:EFF-1 protein, C elegans; D008562:Membrane Glycoproteins; D014760:Viral Fusion Proteins