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纤毛与鞭毛内运输的结构生物学

Structural Biology of Cilia and Intraflagellar Transport.

作者信息

Klena Nikolai, Pigino Gaia

机构信息

Human Technopole, Milan, Italy; email:

出版信息

Annu Rev Cell Dev Biol. 2022 Oct 6;38:103-123. doi: 10.1146/annurev-cellbio-120219-034238. Epub 2022 Jun 29.

Abstract

Cilia are ubiquitous microtubule-based eukaryotic organelles that project from the cell to generate motility or function in cellular signaling. Motile cilia or flagella contain axonemal dynein motors and other complexes to achieve beating. Primary cilia are immotile and act as signaling hubs, with receptors shuttling between the cytoplasm and ciliary compartment. In both cilia types, an intraflagellar transport (IFT) system powered by unique kinesin and dynein motors functions to deliver the molecules required to build cilia and maintain their functions. Cryo-electron tomography has helped to reveal the organization of protein complex arrangement along the axoneme and the structure of anterograde IFT trains as well as the structure of primary cilia. Only recently, single-particle analysis (SPA) cryo-electron microscopy has provided molecular details of the protein organization of ciliary components, helping us to understand how they bind to microtubule doublets and how mechanical force propagated by dynein conformational changes is converted into ciliary beating. Here we highlight recent structural advances that are leading to greater knowledge of ciliary function.

摘要

纤毛是普遍存在的基于微管的真核细胞器,从细胞表面伸出以产生运动或在细胞信号传导中发挥作用。运动性纤毛或鞭毛含有轴丝动力蛋白马达和其他复合物以实现摆动。初级纤毛是不运动的,充当信号枢纽,受体在细胞质和纤毛区室之间穿梭。在这两种类型的纤毛中,由独特的驱动蛋白和动力蛋白马达驱动的鞭毛内运输(IFT)系统发挥作用,来递送构建纤毛并维持其功能所需的分子。冷冻电子断层扫描有助于揭示沿轴丝的蛋白质复合物排列组织以及顺行IFT列车的结构以及初级纤毛的结构。直到最近,单颗粒分析(SPA)冷冻电子显微镜才提供了纤毛成分蛋白质组织的分子细节,帮助我们了解它们如何与微管双联体结合,以及动力蛋白构象变化传播的机械力如何转化为纤毛摆动。在这里,我们重点介绍最近的结构进展,这些进展使我们对纤毛功能有了更多了解。

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