Structure of cellular ESCRT-III spirals and their relationship to HIV budding
Structure of cellular ESCRT-III spirals and their relationship to HIV budding
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DOI：
10.7554/elife.02184
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发表时间：
2014-05-30
期刊：
影响因子：
7.7
通讯作者：
Hanson, Phyllis I.
中科院分区：
文献类型：
--
作者：
Cashikar, Anil G.;Shim, Soomin;Hanson, Phyllis I.
ESCRT机制沿着AAA+ ATP酶Vps 4驱动膜断裂，以在内吞途径中运输到多泡体中，并用于病毒出芽和胞质分裂的拓扑相关过程，但它们如何实现这一点仍不清楚。使用深蚀刻电子显微镜，我们发现，内源性ESCRT-III丝稳定的细胞消耗Vps 4创建均匀的膜变形的锥形螺旋，这是特定的ESCRT-III杂聚物的组件。为了探索ESCRT-III丝的功能作用，我们研究了HIV-1 Gag介导的病毒样颗粒出芽，发现耗尽Vps 4捕获新生Gag组装周围的ESCRT-III丝。观察到的结构之间的插值表明Vps 4在分离ESCRT-III与Gag或其他货物中的新作用，以允许颈部收缩ESCRT-III螺旋的向心生长。
The ESCRT machinery along with the AAA+ ATPase Vps4 drive membrane scission for trafficking into multivesicular bodies in the endocytic pathway and for the topologically related processes of viral budding and cytokinesis, but how they accomplish this remains unclear. Using deep-etch electron microscopy, we find that endogenous ESCRT-III filaments stabilized by depleting cells of Vps4 create uniform membrane-deforming conical spirals which are assemblies of specific ESCRT-III heteropolymers. To explore functional roles for ESCRT-III filaments, we examine HIV-1 Gag-mediated budding of virus-like particles and find that depleting Vps4 traps ESCRT-III filaments around nascent Gag assemblies. Interpolating between the observed structures suggests a new role for Vps4 in separating ESCRT-III from Gag or other cargo to allow centripetal growth of a neck constricting ESCRT-III spiral.