Dynamics of Allosteric Transitions in Dynein
Dynamics of Allosteric Transitions in Dynein
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DOI：
10.1016/j.str.2018.08.005
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发表时间：
2018-12-04
期刊：
影响因子：
5.7
通讯作者：
Thirumalai, D.
中科院分区：
文献类型：
--
作者：
Goldtzvik, Yonathan;Mugnai, Mauro Lorenzo;Thirumalai, D.
细胞质动力蛋白，其运动域属于AAA+家族，在微管上向负端行走。使用不同核苷酸状态下的可用结构，我们进行了粗粒度模型的模拟，以阐明变构转换的动力学。ATP的结合关闭了AAA1和AAA2结构域之间的裂缝，触发了运动结构域其余部分的构象变化，从而形成了前动力中风状态。与微管的相互作用，隐含地建模，提高ADP释放速率，并形成后动力中风状态。连接体（LN）的动力学是不均匀的，它可逆地从直的状态变为弯曲的状态。当ATP与AAA3结合时，LN与AAA2结构域中的插入环之间的持续相互作用防止了动力性卒中前状态的形成，从而将动力蛋白锁定在受抑制的非功能状态。对LN施加机械力可恢复被抑制状态下的运动性。
Cytoplasmic dynein, whose motor domain belongs to the AAA+ family, walks on microtubules toward the minus end. Using the available structures in different nucleotide states, we performed simulations of a coarse-grained model to elucidate the dynamics of allosteric transitions. Binding of ATP closes the cleft between the AAA1 and AAA2 domains, triggering conformational changes in the rest of the motor domain, thus forming the pre-power stroke state. Interactions with the microtubule, modeled implicitly, enhance ADP release rate, and the formation of the post-power stroke state. The dynamics of the linker (LN), which reversibly changes from a straight to a bent state, is heterogeneous. Persistent interactions between the LN and the insert loops in the AAA2 domain prevent the formation of pre-power stroke state when ATP is bound to AAA3, thus locking dynein in a repressed non-functional state. Application of mechanical force to the LN restores motility in the repressed state.