title: The Atlastin C-terminal tail is an amphipathic helix that perturbs the bilayer structure during endoplasmic reticulum homotypic fusion.
abstract: Fusion of tubular membranes is required to form three-way junctions found in reticular subdomains of the endoplasmic reticulum. The large GTPase Atlastin has recently been shown to drive endoplasmic reticulum membrane fusion and three-way junction formation. The mechanism of Atlastin-mediated membrane fusion is distinct from SNARE-mediated membrane fusion, and many details remain unclear. In particular, the role of the amphipathic C-terminal tail of Atlastin is still unknown. We found that a peptide corresponding to the Atlastin C-terminal tail binds to membranes as a parallel α helix, induces bilayer thinning, and increases acyl chain disorder. The function of the C-terminal tail is conserved in human Atlastin. Mutations in the C-terminal tail decrease fusion activity in vitro, but not GTPase activity, and impair Atlastin function in vivo. In the context of unstable lipid bilayers, the requirement for the C-terminal tail is abrogated. These data suggest that the C-terminal tail of Atlastin locally destabilizes bilayers to facilitate membrane fusion.
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston Texas 77005.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Faust
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston Texas 77005.
authors.forename: Tanvi
authors.initials: T
authors.lastname: Desai
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston Texas 77005.
authors.forename: Avani
authors.initials: A
authors.lastname: Verma
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213.
authors.forename: Idil
authors.initials: I
authors.lastname: Ulengin
authors.affiliation: Department of Physics and Astronomy, Rice University, Houston, Texas 77005.
authors.forename: Tzu-Lin
authors.initials: TL
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston Texas 77005.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Moss
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston Texas 77005.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Betancourt-Solis
authors.affiliation: Department of Physics and Astronomy, Rice University, Houston, Texas 77005.
authors.forename: Huey W
authors.initials: HW
authors.lastname: Huang
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213.
authors.forename: Tina
authors.initials: T
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston Texas 77005,. Electronic address: mcnew@rice.edu.
authors.forename: James A
authors.initials: JA
authors.lastname: McNew
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary
chemical_list: D029721:Drosophila Proteins; D008051:Lipid Bilayers; D008565:Membrane Proteins; C440006:ATL1 protein, human; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C543694:atl protein, Drosophila
keywords: Cell Compartmentalization; Endoplasmic Reticulum (ER); FRET; GTPase; Membrane Fusion; Membrane Structure; Neurodegeneration; Phospholipid Vesicle