The Atlastin C-terminal Tail Is an Amphipathic Helix That Perturbs the Bilayer Structure during Endoplasmic Reticulum Homotypic Fusion |
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Authors: | Joseph E Faust Tanvi Desai Avani Verma Idil Ulengin Tzu-Lin Sun Tyler J Moss Miguel A Betancourt-Solis Huey W Huang Tina Lee James A McNew |
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Institution: | From the ‡Department of Biochemistry and Cell Biology, Rice University, Houston Texas 77005, ;the §Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, and ;the ¶Department of Physics and Astronomy, Rice University, Houston, Texas 77005 |
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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. |
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Keywords: | Cell Compartmentalization Endoplasmic Reticulum (ER) FRET GTPase Membrane Fusion Membrane Structure Neurodegeneration Phospholipid Vesicle |
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