Dynein’s directionality is controlled by the angle and length of its stalk
Dynein’s directionality is controlled by the angle and length of its stalk
复制标题
动力蛋白的方向性由其茎的角度和长度控制
作者：
Sinan Can;S. Lacey;Mert Gur;A. Carter;A. Yildiz
细胞骨架马达沿着丝状轨道单向移动的能力对于它们在货物运输、运动性和细胞分裂中的作用至关重要。驱动蛋白和肌球蛋白运动家族有一个亚类，它相对于运动家族的其他部分向微管或肌动蛋白丝的相对端移动1，2，而迄今为止研究的所有动力蛋白运动都只向微管的负端移动3。在低温电子显微镜和分子动力学模拟的指导下，我们试图通过工程化酿酒酵母动力蛋白来理解动力蛋白的方向性的机制，该动力蛋白指向微管的正端。在这里，使用单分子测定，我们表明，延长或缩短的卷曲螺旋柄连接电机的微管控制动力蛋白的螺旋方向性周围的微管。通过改变柄的长度和角度，我们成功地逆转了微管正端的运动。这些修饰的作用是改变动力蛋白连接体相对于微管摆动的方向，而不是逆转马达与微管的不对称解结合。由于动力蛋白柄的长度和角度在物种之间是完全保守的，我们的研究结果为为什么所有的动力蛋白都向微管的负端移动提供了解释。动力蛋白朝向微管负端的运动性由连接马达和微管的卷曲螺旋柄的长度和角度控制。
The ability of cytoskeletal motors to move unidirectionally along filamentous tracks is central to their role in cargo transport, motility and cell division. Kinesin and myosin motor families have a subclass that moves towards the opposite end of the microtubule or actin filament with respect to the rest of the motor family1,2, whereas all dynein motors that have been studied so far exclusively move towards the minus end of the microtubule3. Guided by cryo-electron microscopy and molecular dynamics simulations, we sought to understand the mechanism that underpins the directionality of dynein by engineering a Saccharomyces cerevisiae dynein that is directed towards the plus end of the microtubule. Here, using single-molecule assays, we show that elongation or shortening of the coiled-coil stalk that connects the motor to the microtubule controls the helical directionality of dynein around microtubules. By changing the length and angle of the stalk, we successfully reversed the motility towards the plus end of the microtubule. These modifications act by altering the direction in which the dynein linker swings relative to the microtubule, rather than by reversing the asymmetric unbinding of the motor from the microtubule. Because the length and angle of the dynein stalk are fully conserved among species, our findings provide an explanation for why all dyneins move towards the minus end of the microtubule. The motility of dynein towards the minus end of the microtubule is controlled by the length and angle of the coiled-coil stalk that connects the motor to the microtubule.
影响因子：
5.5
作者：
Best, Robert B.;Zhu, Xiao;Shim, Jihyun;Lopes, Pedro E. M.;Mittal, Jeetain;Feig, Michael;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.
影响因子：
8.8
作者：
Dogan MY;Can S;Cleary FB;Purde V;Yildiz A
通讯作者：
Yildiz A
DOI：
10.1073/pnas.1417422112
发表时间：
2015-05-19
影响因子：
11.1
作者：
Nicholas, Matthew P.;Berger, Florian;Gennerich, Arne
通讯作者：
Gennerich, Arne