Mechanisms of negative membrane curvature sensing and generation by ESCRT III subunit Snf7
Mechanisms of negative membrane curvature sensing and generation by ESCRT III subunit Snf7
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DOI：
10.1002/pro.3851
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发表时间：
2020-03-18
期刊：
影响因子：
8
通讯作者：
Lazaridis, Themis
中科院分区：
文献类型：
--
作者：
Nepal, Binod;Sepehri, Aliasghar;Lazaridis, Themis
某些蛋白质有结合到负弯曲的膜上并产生负曲率的倾向。与那些感知和产生正曲率的蛋白质相比，人们对这些蛋白质的作用机制研究和了解要少得多。在这项工作中，我们使用隐式膜模型来探索一个重要的负曲率感知和产生蛋白质的机制：主要的ESCRT III亚基Snf7。我们发现SnF7单体单独能够感知负曲率，并且对二聚体和三聚体的曲率敏感性增加。我们观察到SnF7齐聚物自发弯曲成圆形结构，择优半径约为20 nm。通过对圆柱膜表面预制螺旋线的模拟，进一步证实了SnF7丝的优先曲率。SNF7纤维不能以相同的界面结合到平面和弯曲的膜上。我们发现，即使细丝具有较好的半径，它在平坦的膜表面上的稳定性也总是不如在内圆柱膜表面上的稳定。这为薄膜弯曲提供了额外的能量，这在螺旋弹簧模型中没有考虑到。此外，圆柱螺旋上的环通过螺旋4桥接在一起，因此与平坦的膜表面上的螺旋相比具有额外的稳定性。
Certain proteins have the propensity to bind to negatively curved membranes and generate negative membrane curvature. The mechanism of action of these proteins is much less studied and understood than those that sense and generate positive curvature. In this work, we use implicit membrane modeling to explore the mechanism of an important negative curvature sensing and generating protein: the main ESCRT III subunit Snf7. We find that Snf7 monomers alone can sense negative curvature and that curvature sensitivity increases for dimers and trimers. We have observed spontaneous bending of Snf7 oligomers into circular structures with preferred radius of similar to 20 nm. The preferred curvature of Snf7 filaments is further confirmed by the simulations of preformed spirals on a cylindrical membrane surface. Snf7 filaments cannot bind with the same interface to flat and curved membranes. We find that even when a filament has the preferred radius, it is always less stable on the flat membrane surface than on the interior cylindrical membrane surface. This provides an additional energy for membrane bending which has not been considered in the spiral spring model. Furthermore, the rings on the cylindrical spirals are bridged together by helix 4 and hence are extra stabilized compared to the spirals on the flat membrane surface.