Structure and disassembly of filaments formed by the ESCRT-III subunit Vps24
Structure and disassembly of filaments formed by the ESCRT-III subunit Vps24
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DOI：
10.1016/j.str.2008.06.010
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发表时间：
2008-09-10
期刊：
影响因子：
5.7
通讯作者：
Williams, Roger L.
中科院分区：
文献类型：
--
作者：
Ghazi-Tabatabai, Sara;Saksena, Suraj;Williams, Roger L.
ESCRT机制介导泛素化跨膜蛋白通过多泡体（MVB）分选到溶酶体，并且还在胞质分裂和病毒出芽中起作用。ESCRT-III亚基是在膜上瞬时组装的亚稳态单体。然而，这些集会的性质尚不清楚。在核心酵母ESCRT-III亚基中，Snf 7和Vps 24在体外自发形成有序聚合物。螺旋状Vps 24细丝的单粒子EM重建显示平行和头对头亚基排列。参与体外分子间组装的区域的突变导致体内货物分选缺陷，这表明这些均聚物模拟MVB生物发生期间由ESCRT-III杂聚物形成的相互作用。Vps 24的C末端位于细丝的表面，并且对于细丝组装是不需要的。当该区域被来自ESCRT-III的Vps 2亚基的MIT相互作用基序取代时，AAA-ATP酶Vps 4可以以核苷酸依赖的方式捆绑和分解嵌合细丝。
The ESCRT machinery mediates sorting of ubiquitinated transmembrane proteins to lysosomes via multivesicular bodies (MVBs) and also has roles in cytokinesis and viral budding. The ESCRT-III subunits are metastable monomers that transiently assemble on membranes. However, the nature of these assemblies is unknown. Among the core yeast ESCRT-III subunits, Snf7 and Vps24 spontaneously form ordered polymers in vitro. Single-particle EM reconstruction of helical Vps24 filaments shows both parallel and head-to-head subunit arrangements. Mutations of regions involved in intermolecular assembly in vitro result in cargo-sorting defects in vivo, suggesting that these homopolymers mimic interactions formed by ESCRT-III heteropolymers during MVB biogenesis. The C terminus of Vps24 is at the surface of the filaments and is not required for filament assembly. When this region is replaced by the MIT-interacting motif from the Vps2 subunit of ESCRT-III, the AAA-ATPase Vps4 can both bundle and disassemble the chimeric filaments in a nucleotide-dependent fashion.