ATP-driven remodeling of the linker domain in the dynein motor.
ATP-driven remodeling of the linker domain in the dynein motor.
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DOI：
10.1016/j.str.2012.07.003
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发表时间：
2012-10-10
期刊：
影响因子：
--
通讯作者：
Burgess SA
中科院分区：
文献类型：
--
作者：
Roberts AJ;Malkova B;Walker ML;Sakakibara H;Numata N;Kon T;Ohkura R;Edwards TA;Knight PJ;Sutoh K;Oiwa K;Burgess SA
动力蛋白ATP酶是已知的最大的细胞骨架马达，在细胞中执行关键功能：沿细胞质中的微管沿着载货物并为鞭毛跳动提供动力。动力蛋白是AAA+环状酶超家族的成员，但人们对它们如何利用这种结构产生运动知之甚少。在这里，我们已经使用冷冻EM来确定3D地图的原生鞭毛动力蛋白-C和细胞质动力蛋白电机域在不同的核苷酸状态。结构显示AAA+环内构象变化的关键位点和“接头”结构域的大重排，涉及其中间附近的铰链。其中接头从环“脱离”的突变体的分析表明接头重塑需要通过与AAA+模块的相互作用提供的能量。将动力蛋白c结构拟合到鞭毛断层图像中表明了这种机制如何驱动微管之间的滑动，并且还对细胞质货物运输具有影响。动力蛋白连接结构域中的铰链作用放大了动力蛋白运动。连接结构是一种稳定的结构，可以被动力蛋白的AAA+模块主动重塑。动力蛋白的颈部亚结构域与AAA 4相互作用，是一个内在的柔性位点。动力蛋白是AAA+马达蛋白，为微管运输和鞭毛运动提供动力。罗伯茨等人目前cryo-EM结构的两类动力蛋白，揭示核苷酸诱导的弯曲，并表明动力蛋白产生的运动，通过使用AAA+环，积极改造自己的连接器。
Dynein ATPases are the largest known cytoskeletal motors and perform critical functions in cells: carrying cargo along microtubules in the cytoplasm and powering flagellar beating. Dyneins are members of the AAA+ superfamily of ring-shaped enzymes, but how they harness this architecture to produce movement is poorly understood. Here, we have used cryo-EM to determine 3D maps of native flagellar dynein-c and a cytoplasmic dynein motor domain in different nucleotide states. The structures show key sites of conformational change within the AAA+ ring and a large rearrangement of the “linker” domain, involving a hinge near its middle. Analysis of a mutant in which the linker “undocks” from the ring indicates that linker remodeling requires energy that is supplied by interactions with the AAA+ modules. Fitting the dynein-c structures into flagellar tomograms suggests how this mechanism could drive sliding between microtubules, and also has implications for cytoplasmic cargo transport. ► Structural changes in axonemal and cytoplasmic dynein motors seen by cryo-EM ► Movement is amplified by a hinge action within dynein's linker domain ► The linker is a stable structure that is actively remodeled by dynein's AAA+ modules ► Dynein's neck subdomain interacts with AAA4 and is an intrinsic site of flexibility Dyneins are AAA+ motor proteins that power both microtubule-based transport and flagellar motility. Now, Roberts et al. present cryo-EM structures of both classes of dynein, revealing nucleotide-induced bending and indicating that dynein generates movement by using the AAA+ ring to actively remodel its own linker.
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