The Atlastin C-terminal Tail Is an Amphipathic Helix That Perturbs the Bilayer Structure during Endoplasmic Reticulum Homotypic Fusion
The Atlastin C-terminal Tail Is an Amphipathic Helix That Perturbs the Bilayer Structure during Endoplasmic Reticulum Homotypic Fusion
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DOI：
10.1074/jbc.m114.601823
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发表时间：
2015-02-20
影响因子：
4.8
通讯作者：
McNew, James A.
中科院分区：
文献类型：
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作者：
Faust, Joseph E.;Desai, Tanvi;McNew, James A.
管状膜的融合需要形成内质网网状亚域中的三路连接。最近已证明大型 GTP 酶 Atlastin 可以驱动内质网膜融合和三路连接形成。 Atlastin介导的膜融合机制与SNARE介导的膜融合不同，许多细节仍不清楚。特别是，Atlastin 的两亲性 C 末端尾部的作用仍不清楚。我们发现，对应于 Atlastin C 末端尾部的肽以平行 α 螺旋的形式与膜结合，诱导双层变薄，并增加酰基链紊乱。 C 末端尾部的功能在人 Atlastin 中是保守的。 C 末端尾部的突变会降低体外融合活性，但不会降低 GTPase 活性，并损害体内 Atlastin 功能。在脂质双层不稳定的情况下，对 C 端尾部的要求被废除。这些数据表明 Atlastin 的 C 末端尾部局部破坏双层的稳定性以促进膜融合。
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 alpha 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.