Intrinsically disordered proteins drive membrane curvature.
Intrinsically disordered proteins drive membrane curvature.
复制标题
DOI：
10.1038/ncomms8875
复制
发表时间：
2015-07-24
影响因子：
16.6
通讯作者：
Stachowiak JC
中科院分区：
文献类型：
--
作者：
Busch DJ;Houser JR;Hayden CC;Sherman MB;Lafer EM;Stachowiak JC
高度弯曲的膜结构的组装对于细胞生理学是必不可少的。普遍的观点是，蛋白质的曲率促进结构基序，如楔形两亲性螺旋和新月形BAR域，是弯曲膜所必需的。在这里，我们报告说，内在的无序结构域的内吞衔接蛋白，Epsin1和AP180是非常有效的驱动器的膜曲率。这个结果是出乎意料的，因为本质上无序的域缺乏明确定义的三维结构。然而，在体外测量的膜曲率和蛋白质扩散表明，这些域的大的流体动力学半径产生的空间压力，驱动膜弯曲。当无序衔接域在哺乳动物细胞中表达为跨膜货物时，它们被排除在网格蛋白包被的凹坑之外。我们建议，膜的两个表面上的空间压力的平衡驱动这种排斥。这些结果为空间压力对弯曲细胞膜结构的含量和组装的影响提供了定量证据。 使膜弯曲的蛋白质通常含有促进曲率的结构基序，如楔形或新月形结构域。Busch等人报道，本质上无序的结构域也可以驱动膜弯曲，并提供了蛋白质拥挤驱动的空间压力介导这种效应的证据。
Assembly of highly curved membrane structures is essential to cellular physiology. The prevailing view has been that proteins with curvature-promoting structural motifs, such as wedge-like amphipathic helices and crescent-shaped BAR domains, are required for bending membranes. Here we report that intrinsically disordered domains of the endocytic adaptor proteins, Epsin1 and AP180 are highly potent drivers of membrane curvature. This result is unexpected since intrinsically disordered domains lack a well-defined three-dimensional structure. However, in vitro measurements of membrane curvature and protein diffusivity demonstrate that the large hydrodynamic radii of these domains generate steric pressure that drives membrane bending. When disordered adaptor domains are expressed as transmembrane cargo in mammalian cells, they are excluded from clathrin-coated pits. We propose that a balance of steric pressure on the two surfaces of the membrane drives this exclusion. These results provide quantitative evidence for the influence of steric pressure on the content and assembly of curved cellular membrane structures. Proteins that bend membranes often contain curvature-promoting structural motifs such as wedges or crescent-shaped domains. Busch et al. report that intrinsically disordered domains can also drive membrane curvature and provide evidence that steric pressure driven by protein crowding mediates this effect.