Shemesh Tom, Otomo Takanori, Rosen Michael K, Bershadsky Alexander D, Kozlov Michael M
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.
J Cell Biol. 2005 Sep 12;170(6):889-93. doi: 10.1083/jcb.200504156.
The FH2 domains of formin family proteins act as processive cappers of actin filaments. Previously suggested stair-stepping mechanisms of processive capping imply that a formin cap rotates persistently in one direction with respect to the filament. This challenges the formin-mediated mechanism of intracellular cable formation. We suggest a novel scenario of processive capping that is driven by developing and relaxing torsion elastic stresses. Based on the recently discovered crystal structure of an FH2-actin complex, we propose a second mode of processive capping-the screw mode. Within the screw mode, the formin dimer rotates with respect to the actin filament in the direction opposite to that generated by the stair-stepping mode so that a combination of the two modes prevents persistent torsion strain accumulation. We determine an optimal regime of processive capping, whose essence is a periodic switch between the stair-stepping and screw modes. In this regime, elastic energy does not exceed feasible values, and supercoiling of actin filaments is prevented.
formin家族蛋白的FH2结构域作为肌动蛋白丝的持续封端蛋白。先前提出的持续封端的阶梯式机制表明，formin帽相对于肌动蛋白丝沿一个方向持续旋转。这对formin介导的细胞内电缆形成机制提出了挑战。我们提出了一种由发展和松弛扭转弹性应力驱动的持续封端新场景。基于最近发现的FH2-肌动蛋白复合物的晶体结构，我们提出了持续封端的第二种模式——螺旋模式。在螺旋模式中，formin二聚体相对于肌动蛋白丝沿与阶梯式模式产生的方向相反的方向旋转，从而两种模式的组合可防止持续的扭转应变积累。我们确定了持续封端的最佳状态，其本质是阶梯式模式和螺旋模式之间的周期性切换。在这种状态下，弹性能量不会超过可行值，并且可防止肌动蛋白丝的超螺旋化。
