Structure and assembly of the A-C linker connecting microtubule triplets in centrioles

IF 12.5 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Bin Cai, Jingwei Xu, Erik H. Collet, Ellen Aarts, Leo Luo, Alexander Leitner, Takashi Ishikawa, Pedro Beltrao, Chad G. Pearson, Martin Pilhofer, Michal Wieczorek
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Abstract

Centriole assembly involves the coordination of centriolar modules. One module is the A-C linker, an enigmatic protein assembly connecting the A-microtubule of one microtubule triplet to the C-microtubule of the neighboring triplet. Here, we integrated biochemistry, multiscale cryo–electron microscopy, and AlphaFold modeling to investigate the architecture of the centriole. Using an improved centriole isolation method, we determined the structure of the A-C linker bound to microtubule triplets, which revealed how the A-C linker cross-links microtubules and integrates with the B-C junction. We found marked changes in the structure and composition of the A-C linker that correlate with the presence of other centriolar modules, including the pinhead, cartwheel, and inner scaffold. Our findings show that the A-C linker is a highly integrated component of the centriole whose polymorphism may orchestrate the assembly of spatially distinct centriolar modules, and provide a framework for dissecting the biology of centrioles.

Abstract Image

中心粒中连接微管三重体的A-C连接体的结构和组装
中心粒组装涉及到中心粒模块的协调。其中一个模块是A-C连接器,这是一种神秘的蛋白质组装,将一个微管三重态的a微管连接到邻近三重态的c微管。在这里,我们结合了生物化学、多尺度冷冻电子显微镜和AlphaFold模型来研究中心粒的结构。利用改进的中心粒分离方法,我们确定了A-C连接子与微管三联体结合的结构,揭示了A-C连接子是如何交联微管并与B-C连接结合的。我们发现A-C连接体的结构和组成发生了显著变化,这与其他向心模块的存在有关,包括针头、侧轮和内支架。我们的研究结果表明,a - c连接体是中心粒的一个高度集成的组成部分,其多态性可能协调了空间上不同的中心粒模块的组装,并为剖析中心粒的生物学提供了一个框架。
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来源期刊
Science Advances
Science Advances 综合性期刊-综合性期刊
CiteScore
21.40
自引率
1.50%
发文量
1937
审稿时长
29 weeks
期刊介绍: Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.
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