Structure of the radial spoke head and insights into its role in mechanoregulation of ciliary beating.

Structure of the radial spoke head and insights into its role in mechanoregulation of ciliary beating.
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径向辐条头的结构及其在纤毛跳动机械调节中的作用的见解。

DOI:
10.1038/s41594-020-00519-9
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发表时间:
2021-01
影响因子:
16.8
通讯作者:
Vale RD
Vale RD
中科院分区:
生物学1区
文献类型:
--
作者:
Grossman-Haham I;Coudray N;Yu Z;Wang F;Zhang N;Bhabha G;Vale RD

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运动纤毛为细胞运动提供动力,并通过将弯曲波从其基部传播到尖端来驱动细胞外液体流动。纤毛的协调弯曲需要径向辐条(RS)蛋白复合物和微管中心对(CP)的机械调节。尽管它们对真核生物的纤毛运动很重要,但RSs的分子功能尚不清楚。在这里,我们重建了靠近CP的莱茵衣藻RS头,并使用3.1 Å分辨率的单粒子冷冻电镜(cro - em)确定了其结构,揭示了由紧密缠绕的蛋白质刚性核心支撑的扁平带负电的表面。这个核心的突变,与人类纤毛病相关的突变相对应,破坏了重组复合物的稳定性,为疾病提供了分子基础。部分逆转RS表面的负电荷会损害莱茵草的运动能力。我们提出RS头部结构非常适合通过与CP的物理碰撞来进行纤毛跳动的机械调节。
Motile cilia power cell locomotion and drive extracellular fluid flow by propagating bending waves from their base to tip. The coordinated bending of cilia requires mechanoregulation by the radial spoke (RS) protein complexes and the microtubule central pair (CP). Despite their importance for ciliary motility across eukaryotes, the molecular function of the RSs is unknown. Here, we reconstituted the Chlamydomonas reinhardtii RS head that abuts the CP and determined its structure using single-particle cryo-EM to 3.1 Å resolution, revealing a flat, negatively-charged surface supported by a rigid core of tightly intertwined proteins. Mutations in this core, corresponding to those involved in human ciliopathies, compromised stability of the recombinant complex, providing a molecular basis for disease. Partially reversing the negative charge on the RS surface impaired motility in C. reinhardtii. We propose that the RS head architecture is well-suited for mechanoregulation of ciliary beating through physical collisions with the CP.
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