Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Department of Biochemistry, University of Geneva, CH-1211 Geneva, Switzerland.
Proc Natl Acad Sci U S A. 2019 Jun 25;116(26):12845-12850. doi: 10.1073/pnas.1903769116. Epub 2019 Jun 12.
Dynamin proteins assemble into characteristic helical structures around necks of clathrin-coated membrane buds. Hydrolysis of dynamin-bound GTP results in both fission of the membrane neck and partial disruption of the dynamin oligomer. Imaging by atomic force microscopy reveals that, on GTP hydrolysis, dynamin oligomers undergo a dynamic remodeling and lose their distinctive helical shape. While breakup of the dynamin helix is a critical stage in clathrin-mediated endocytosis, the mechanism for this remodeling of the oligomer has not been resolved. In this paper, we formulate an analytical, elasticity-based model for the reshaping and disassembly of the dynamin scaffold. We predict that the shape of the oligomer is modulated by the orientation of dynamin's pleckstrin homology (PH) domain relative to the underlying membrane. Our results indicate that tilt of the PH domain drives deformation and fragmentation of the oligomer, in agreement with experimental observations. This model motivated the introduction of the tilted helix: a curve that maintains a fixed angle between its normal and the normal of the embedding surface. Our findings highlight the importance of tilt as a key regulator of size and morphology of membrane-bound oligomers.
动力蛋白蛋白在网格蛋白包被膜泡的颈部周围组装成特征性的螺旋结构。动力蛋白结合的 GTP 的水解导致膜颈部的分裂和动力蛋白寡聚物的部分破坏。原子力显微镜的成像显示，在 GTP 水解时，动力蛋白寡聚物经历动态重塑，失去其独特的螺旋形状。虽然动力蛋白螺旋的解体是网格蛋白介导的胞吞作用的一个关键阶段，但这种寡聚物重塑的机制尚未解决。在本文中，我们为动力蛋白支架的重塑和拆卸制定了一个基于弹性的分析模型。我们预测寡聚物的形状是由动力蛋白的 PH 结构域相对于基底膜的取向来调节的。我们的结果表明，PH 结构域的倾斜驱动了寡聚物的变形和碎片化，这与实验观察结果一致。该模型启发了倾斜螺旋的引入：一条曲线，其法线与嵌入表面的法线之间保持固定角度。我们的研究结果强调了倾斜作为调节膜结合寡聚物大小和形态的关键因素的重要性。
