Department of Chemistry, City College of New York, New York, New York, USA.
Graduate Programs in Chemistry, Biochemistry, and Physics, The Graduate Center, City University of New York, New York, New York, USA.
Protein Sci. 2020 Jun;29(6):1473-1485. doi: 10.1002/pro.3851. Epub 2020 Mar 18.
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.
某些蛋白质具有结合负曲率膜并产生负膜曲率的倾向。这些蛋白质的作用机制比那些感知和产生正曲率的蛋白质研究和理解得要少得多。在这项工作中，我们使用隐式膜建模来探索一种重要的负曲率感应和产生蛋白的作用机制：主要的 ESCRT III 亚基 Snf7。我们发现 Snf7 单体本身可以感应负曲率，并且二聚体和三聚体的曲率敏感性增加。我们观察到 Snf7 低聚物自发弯曲成具有~20nm 左右优选半径的圆形结构。Snf7 纤维的优选曲率进一步通过在圆柱形膜表面上模拟预先形成的螺旋得到证实。Snf7 纤维不能用相同的界面与平面和弯曲的膜结合。我们发现，即使纤维具有优选半径，它在平面膜表面上的稳定性也总是低于圆柱内表面。这为螺旋弹簧模型中未考虑的膜弯曲提供了额外的能量。此外，圆柱形螺旋上的环由螺旋 4 桥接在一起，因此与平面膜表面上的螺旋相比更加稳定。
