Cryo-EM structure of an active central apparatus.

Cryo-EM structure of an active central apparatus.
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DOI:
10.1038/s41594-022-00769-9
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发表时间:
2022-05
影响因子:
16.8
通讯作者:
Zhang, Kai
Zhang, Kai
中科院分区:
生物学1区
文献类型:
--
作者:
Han, Long;Rao, Qinhui;Yang, Renbin;Wang, Yue;Chai, Pengxin;Xiong, Yong;Zhang, Kai

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纤毛在时间和空间上的精确调控对细胞的各种活动至关重要,这些活动影响着几乎所有真核生物的生存和发育。一个重要的跳动调节器是运动纤毛的保守的中央装置(CA),由一对微管(C1和C2)组成,每个重复单位与数百个蛋白质亚基相关。CA如何在纤毛运动中发挥其调节作用尚不清楚。在这里,我们提出了高分辨率结构的衣原体reinhardtii CA冷冻电子显微镜(cryo-EM)和它的动态构象行为在多个尺度。这些结构显示了CA的功能相关的投射蛋白如何聚集在弹簧状的犰狳重复蛋白支架上,这是由细长的脊柱样蛋白促成的。CA的两个半部分通过弹性链状桥蛋白连接在一起,以实现协调的活动。我们在两种不同的步进状态下捕获了驱动蛋白样蛋白(KLP 1)的阵列,这与纤毛的拍波传播密切相关。这些发现为理解CA在纤毛中的作用建立了一个结构框架。在这里,作者解决冷冻电镜结构的中央装置的运动纤毛,并分析其动态构象,以阐明纤毛跳动的机制。
Accurately regulated ciliary beating in time and space is critical for diverse cellular activities, which impact the survival and development of nearly all eukaryotic species. An essential beating regulator is the conserved central apparatus (CA) of motile cilia, composed of a pair of microtubules (C1 and C2) associated with hundreds of protein subunits per repeating unit. It is largely unclear how the CA plays its regulatory roles in ciliary motility. Here, we present high-resolution structures of Chlamydomonas reinhardtii CA by cryo-electron microscopy (cryo-EM) and its dynamic conformational behavior at multiple scales. The structures show how functionally related projection proteins of CA are clustered onto a spring-shaped scaffold of armadillo-repeat proteins, facilitated by elongated rachis-like proteins. The two halves of the CA are brought together by elastic chain-like bridge proteins to achieve coordinated activities. We captured an array of kinesin-like protein (KLP1) in two different stepping states, which are actively correlated with beating wave propagation of cilia. These findings establish a structural framework for understanding the role of the CA in cilia. Here, authors solve cryo-EM structures of the central apparatus of motile cilia and analyze its dynamic conformations to elucidate the mechanism of ciliary beating.
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