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Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes

机译:ESCRT-III / VPS4膜重塑和裂变复合物的结构,功能和动力学

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摘要

The endosomal sorting complexes required for transport (ESCRT) pathway mediates cellular membrane remodeling and fission reactions. The pathway comprises five core complexes: ALIX, ESCRT-I, ESCRT-II, ESCRT-III, and Vps4. These soluble complexes are typically recruited to target membranes by site-specific adaptors that bind one or both of the early-acting ESCRTfactors: ALIX andESCRT-I/ESCRT-II. These factors, in turn, nucleate assembly of ESCRT-III subunits into membrane-bound filaments that recruit theAAAATPase Vps4. Together, ESCRT-III filaments and Vps4 remodel and sever membranes. Here, we review recent advances in our understanding of the structures, activities, and mechanisms of the ESCRT-III and Vps4 machinery, including the first high-resolution structures of ESCRT-III filaments, the assembled Vps4 enzyme in complex with an ESCRT-III substrate, the discovery that ESCRT-III/Vps4 complexes can promote both inside-out and outside-in membrane fission reactions, and emerging mechanistic models for ESCRT-mediated membrane fission.
机译:运输(ESCRT)途径所需的内体分选复合物介导细胞膜重塑和裂变反应。该途径包括五个核心复合物:Alix,Escrt-i,Escrt-II,Escrt-III和VPS4。这些可溶性配合物通常通过结合早期的Escrtfortors中的一种或两种的特异性特异性适配器募集至靶膜:Alix Andescrt-I / EscrT-II。反过来,这些因素反过来,将Escrt-III亚基组装成核心核心的膜结合细丝。一起,Escrt-III丝和VPS4重塑和切片膜。在这里,我们审查了我们对ESCRT-III和VPS4机械的结构,活动和机制的理解,包括ESCRT-III长丝的第一个高分辨率结构,组合于ESCRT-III中的组装VPS4酶底物,发现ESCRT-III / VPS4配合物可以促进内外和外部膜裂变反应,以及用于Escrt介导的膜裂变的新出现的机械模型。

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