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Mechanisms of negative membrane curvature sensing and generation by ESCRT III subunit Snf7.
Protein Science ( IF 4.5 ) Pub Date : 2020-03-06 , DOI: 10.1002/pro.3851
Binod Nepal 1 , Aliasghar Sepehri 1 , Themis Lazaridis 1, 2
Affiliation  

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 ~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.

中文翻译:

ESCRT III亚基Snf7产生负膜曲率的机制。

某些蛋白质倾向于与负弯曲膜结合并产生负膜曲率。与感知并产生正曲率的蛋白质相比,对这些蛋白质的作用机理的研究和了解少得多。在这项工作中,我们使用隐式膜建模来探索重要的负曲率感测和生成蛋白质的机制:主要的ESCRT III亚基Snf7。我们发现单独的Snf7单体可以感应负曲率,并且对于二聚体和三聚体,曲率灵敏度会提高。我们已经观察到Snf7低聚物自发弯曲成圆形结构,其优选半径约为20 nm。Snf7细丝的最佳曲率进一步通过在圆柱形膜表面上预先形成的螺旋的模拟得到了证实。Snf7细丝不能以相同的界面结合到平坦和弯曲的膜上。我们发现,即使细丝具有优选的半径,其在平坦膜表面上的稳定性也总是比内部圆柱形膜表面上的稳定性差。这为膜弯曲提供了额外的能量,这在螺旋弹簧模型中并未考虑。此外,圆柱形螺旋上的环通过螺旋4桥接在一起,因此与平膜表面上的螺旋相比更加稳定。
更新日期:2020-03-06
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