Structure and membrane remodeling activity of ESCRT-III helical polymers.
Structure and membrane remodeling activity of ESCRT-III helical polymers.
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DOI：
10.1126/science.aad8305
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发表时间：
2015-12-18
期刊：
影响因子：
--
通讯作者：
Frost A
中科院分区：
文献类型：
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作者：
McCullough J;Clippinger AK;Talledge N;Skowyra ML;Saunders MG;Naismith TV;Colf LA;Afonine P;Arthur C;Sundquist WI;Hanson PI;Frost A
运输所需的内体分选复合物（ESCRT）蛋白介导需要稳定负膜曲率的基本膜重塑事件。这些包括核内体腔内小泡形成、HIV出芽、核膜闭合和细胞动力学分裂。ESCRT-III亚基通过改变构象和聚合成膜重塑丝在这些过程中发挥关键作用。在这里，我们报告的4倍分辨率cryo-EM重建的一个开始，双链螺旋共聚物组成的两个不同的人类ESCRT-III亚基，CHMP 1B和IST 1。内链包含“开放”CHMP 1B亚基，其在精心设计的结构域交换结构中互锁，并且被“封闭”IST 1亚基的外链包围。与其他ESCRT-III蛋白不同，CHMP 1B和IST 1聚合物在体外和体内均在正弯曲膜上形成外涂层。我们的分析表明，常见的ESCRT-III细丝结构可以稳定不同程度和方向的膜曲率。
The Endosomal Sorting Complexes Required for Transport (ESCRT) proteins mediate fundamental membrane remodeling events that require stabilizing negative membrane curvature. These include endosomal intralumenal vesicle formation, HIV budding, nuclear envelope closure and cytokinetic abscission. ESCRT-III subunits perform key roles in these processes by changing conformation and polymerizing into membrane-remodeling filaments. Here, we report the 4 Å resolution cryo-EM reconstruction of a one-start, double-stranded helical copolymer composed of two different human ESCRT-III subunits, CHMP1B and IST1. The inner strand comprises “open” CHMP1B subunits that interlock in an elaborate domain-swapped architecture, and is encircled by an outer strand of “closed” IST1 subunits. Unlike other ESCRT-III proteins, CHMP1B and IST1 polymers form external coats on positively-curved membranes in vitro and in vivo. Our analysis suggests how common ESCRT-III filament architectures could stabilize different degrees and directions of membrane curvature.