Transitions in filament geometry drive ESCRT-III-mediated membrane remodelling and fission
Transitions in filament geometry drive ESCRT-III-mediated membrane remodelling and fission
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丝几何结构的转变驱动 ESCRT-III 介导的膜重塑和裂变
DOI：
10.1101/559898
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Harker-Kirschneck L
中科院分区：
文献类型：
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作者：
Harker-Kirschneck L
ESCRT-III 是一种进化上保守的膜重塑机制，与 Vps4 ATP 酶一起形成能够从胞质侧切割生物膜的细丝。 ESCRT-III 的这种活性对于古细菌和许多真核生物细胞分裂的最后阶段、囊泡的形成、外泌体的产生、HIV-1 和埃博拉等病毒的释放以及细胞膜的修复和密封至关重要。虽然最近在描述不同 ESCRT-III 功能的生化和细胞生物学细节方面取得了快速进展，但我们对 ESCRT-III 介导的膜重塑所涉及的物理机制缺乏了解。在这里，通过粗粒度分子动力学模拟的发展，我们提出了一个最小模型，该模型捕获了 ESCRT-III 诱导实验报告的 ESCRT-III 驱动膜雕刻案例的能力，包括锥体和小管的形成以及膜分裂。该模型提出了一种与其他细胞骨架元件不同的通用物理作用机制，即膜结合的 ESCRT-III 丝扭转的变化驱动扁平螺旋和 3D 螺旋之间的转变，从而诱导膜变形和断裂。我们期望这里揭示的机械原理可用于操纵细胞中 ESCRT-III 驱动的过程以及指导合成膜雕刻系统的工程。
ESCRT-III is an evolutionarily conserved membrane remodeling machinery that, with the Vps4 ATPase, forms filaments able to cut biological membranes from the cytosolic side. This activity of ESCRT-III is essential for the final stage of cell division in archaea and in many eukaryotes, the formation of vesicles, the creation of exosomes, the release of viruses such as HIV-1 and Ebola, and for the repair and sealing of cellular membranes. While there has been recent rapid progress in describing the biochemical and cell biology details of different ESCRT-III functions, we lack an understanding of the physical mechanism involved in ESCRT-III-mediated membrane remodelling. Here, through the development of coarse-grained molecular dynamic simulations, we present a minimal model that captures the ability of ESCRT-III to induce experimentally reported cases of ESCRT-III driven membrane sculpting, including the formation of cones and tubules, and membrane scission. This model suggests a universal physical mechanism of action, that differs from that of other cytoskeletal elements, whereby a change in the twist of membrane bound ESCRT-III filaments drives transitions between a flat spiral and a 3D helix to induce membrane deformation and scission. We expect the mechanistic principles revealed here to be useful in manipulating ESCRT-III-driven processes in cells and in guiding the engineering of synthetic membrane-sculpting systems.