首页> 美国卫生研究院文献>The Journal of Biological Chemistry >The Atlastin C-terminal Tail Is an Amphipathic Helix That Perturbs the Bilayer Structure during Endoplasmic Reticulum Homotypic Fusion
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The Atlastin C-terminal Tail Is an Amphipathic Helix That Perturbs the Bilayer Structure during Endoplasmic Reticulum Homotypic Fusion

机译:Atlastin C末端尾巴是内质网同型融合过程中干扰双层结构的两亲性螺旋。

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摘要

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.
机译:需要管状膜的融合以形成在内质网的网状亚结构域中发现的三向连接。大型GTPase Atlastin最近被证明可驱动内质网膜融合和三向连接形成。 Atlastin介导的膜融合机制不同于SNARE介导的膜融合,许多细节仍不清楚。特别是,Atlastin的两亲性C末端尾巴的作用仍然未知。我们发现,对应于Atlastin C末端尾巴的肽以平行的α螺旋结合到膜上,诱导双层变薄,并增加了酰基链紊乱。 C端尾巴的功能在人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,并且会削弱体内的Atlastin功能。在不稳定的脂质双层的情况下,取消了对C-末端尾部的要求。这些数据表明,Atlastin的C末端尾部会局部破坏双层的稳定性,从而促进膜融合。

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