Structures of outer-arm dynein array on microtubule doublet reveal a motor coordination mechanism.
Structures of outer-arm dynein array on microtubule doublet reveal a motor coordination mechanism.
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DOI：
10.1038/s41594-021-00656-9
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发表时间：
2021-10
影响因子：
16.8
通讯作者：
Zhang K
中科院分区：
文献类型：
--
作者：
Rao Q;Han L;Wang Y;Chai P;Kuo YW;Yang R;Hu F;Yang Y;Howard J;Zhang K
成千上万的外臂动力蛋白（OAD）排列在轴丝中，以驱动有节奏的纤毛跳动。多个OAD之间的协调对于产生机械力以弯曲微管对（MTD）是必不可少的。使用电子显微镜，我们确定了高分辨率结构的四膜虫嗜热OAD阵列绑定到MTD在两个不同的状态。OAD优先结合MTD原丝的模式类似于其独特的微管结合域的天然轨道。在MTD结合后，诱导游离OAD采取稳定的平行构象，引发阵列形成。广泛的尾到头（TTH）OAD之间的相互作用被观察到，这需要被打破的ATP周转动力蛋白电机。我们建议阵列中的OAD依次水解ATP以滑动MTD。ATP水解反过来松弛TTH界面，以影响下游OAD的游离核苷酸循环。这些发现导致一个模型，解释如何在轴丝构象变化产生协调行动的动力蛋白。外臂动力蛋白（OAD）在纤毛轴丝上组装成大阵列以驱动有节奏的跳动。冷冻电镜结构的微管结合嗜热四膜虫OAD阵列揭示了这个复杂的组装细节，并提出了一个模型，其协调行动的机制。
Thousands of outer-arm dyneins (OADs) are arrayed in the axoneme to drive a rhythmic ciliary beat. Coordination among multiple OADs is essential for generating mechanical forces to bend microtubule doublets (MTDs). Using electron microscopy, we determined high-resolution structures of Tetrahymena thermophila OAD arrays bound to MTDs in two different states. OAD preferentially binds to MTD protofilaments with a pattern resembling the native tracks for its distinct microtubule-binding domains. Upon MTD binding, free OADs are induced to adopt a stable parallel conformation, primed for array formation. Extensive tail-to-head (TTH) interactions between OADs are observed, which need to be broken for ATP turnover by the dynein motor. We propose that OADs in an array sequentially hydrolyze ATP to slide the MTDs. ATP hydrolysis in turn relaxes the TTH interfaces to effect free nucleotide cycles of downstream OADs. These findings lead to a model explaining how conformational changes in the axoneme produce coordinated action of dyneins. Outer-arm dyneins (OADs) assemble in large arrays on the ciliary axoneme to drive rhythmic beating. Cryo-EM structures of microtubule-bound Tetrahymena thermophila OAD arrays reveal details of this complex assembly and suggest a model for its mechanism of coordinated action.
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影响因子：
3.3
作者：
Ichikawa M;Saito K;Yanagisawa HA;Yagi T;Kamiya R;Yamaguchi S;Yajima J;Kushida Y;Nakano K;Numata O;Toyoshima YY
通讯作者：
Toyoshima YY
影响因子：
3.3
作者：
Kubo T;Hou Y;Cochran DA;Witman GB;Oda T
通讯作者：
Oda T
影响因子：
48
作者：
Kastner, Berthold;Fischer, Niels;Stark, Holger
通讯作者：
Stark, Holger
DOI：
10.1126/science.1164424
发表时间：
2008-12-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carter AP;Garbarino JE;Wilson-Kubalek EM;Shipley WE;Cho C;Milligan RA;Vale RD;Gibbons IR
通讯作者：
Gibbons IR
影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ