Curvature of clathrin-coated pits driven by epsin
Curvature of clathrin-coated pits driven by epsin
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DOI：
10.1038/nature01020
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发表时间：
2002-09-26
期刊：
影响因子：
64.8
通讯作者：
McMahon, HT
中科院分区：
文献类型：
--
作者：
Ford, MGJ;Mills, IG;McMahon, HT
网状蛋白介导的内吞作用包括货物的选择和膜在蛋白质外壳的辅助下萌发成囊泡。质膜凹坑的形成和随后小泡的萌发是一个能量要求很高的过程，涉及到网状蛋白与许多不同蛋白质的合作。在这里，我们研究了大脑丰富的蛋白质epsin 1在这一过程中的作用。Epsin通过结合膜脂磷脂酰肌醇-4，5-二磷酸(PtdIns(4，5)P-2)来靶向内吞作用的区域。在这里，我们展示了epsin 1在与PtdIns(4，5)P-2结合时直接改变膜的曲率，并结合分子筛聚合。我们发现在epsin中形成的两亲性α-螺旋与PtdIns(4，5)P-2结合是偶联的。这种螺旋疏水区域残基的突变会使膜失去弯曲的能力。我们认为这个螺旋插入到脂质双层的一个小叶中，诱导弯曲。在脂单分子层上，单靠内切酶就足以促进网状蛋白包裹的内陷的形成。
Clathrin-mediated endocytosis involves cargo selection and membrane budding into vesicles with the aid of a protein coat. Formation of invaginated pits on the plasma membrane and subsequent budding of vesicles is an energetically demanding process that involves the cooperation of clathrin with many different proteins. Here we investigate the role of the brain-enriched protein epsin 1 in this process. Epsin is targeted to areas of endocytosis by binding the membrane lipid phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5) P-2). We show here that epsin 1 directly modifies membrane curvature on binding to PtdIns(4,5) P-2 in conjunction with clathrin polymerization. We have discovered that formation of an amphipathic alpha-helix in epsin is coupled to PtdIns(4,5)P-2 binding. Mutation of residues on the hydrophobic region of this helix abolishes the ability to curve membranes. We propose that this helix is inserted into one leaflet of the lipid bilayer, inducing curvature. On lipid monolayers epsin alone is sufficient to facilitate the formation of clathrin-coated invaginations.