美国圣路易斯华盛顿大学Rui Zhang等研究人员合作揭示哺乳动物运动纤毛的轴丝结构多样性。这一研究成果于2025年1月1日在线发表在国际学术期刊《自然》上。

研究人员利用冷冻电子显微镜、冷冻电子断层扫描和蛋白质组学技术，解析了来自精子鞭毛和输卵管、脑室以及呼吸道上皮纤毛的轴丝双微管（DMT）的96纳米模块化重复结构。研究人员发现精子DMT是最具特化性的，而上皮纤毛在不同组织之间仅有轻微差异。研究人员构建了哺乳动物精子DMT的模型，定义了181个蛋白质的定位和相互作用，包括34个新发现的蛋白质。

研究人员阐明了径向辐条3的组成，并揭示了与ATP再生和纤毛运动调节相关的激酶结合位点。研究人员发现了一种特异于精子的轴丝连接的T-复合体蛋白环复合物（TRiC）伴侣蛋白，这可能有助于哺乳动物精子长鞭毛的构建或维持。研究人员解析了轴丝动力蛋白在其前冲状态下的构象变化，进而揭示了纤毛运动过程中发生的构象变化。

这些研究结果说明了化学和机械调节的元件如何嵌入到轴丝内，为理解纤毛病和不孕不育的病因提供了宝贵的资源，同时也展示了现代结构生物学的发现力量。

据介绍，生殖、发育和稳态依赖于运动纤毛，其有节奏的摆动由一种基于微管的分子机器——轴突体提供动力。尽管已有关于绿藻Chlamydomonas reinhardtii轴突体的原子模型，但哺乳动物轴丝的结构仍不完整。此外，人们尚未完全了解轴丝的分子结构如何在体内不同类型的运动纤毛细胞中变化。

附：英文原文

Title: Structural diversity of axonemes across mammalian motile cilia

Author: Leung, Miguel Ricardo, Sun, Chen, Zeng, Jianwei, Anderson, Jacob R., Niu, Qingwei, Huang, Wei, Noteborn, Willem E. M., Brown, Alan, Zeev-Ben-Mordehai, Tzviya, Zhang, Rui

Issue&Volume: 2025-01-01

Abstract: Reproduction, development and homeostasis depend on motile cilia, whose rhythmic beating is powered by a microtubule-based molecular machine called the axoneme. Although an atomic model of the axoneme is available for the alga Chlamydomonas reinhardtii1, structures of mammalian axonemes are incomplete1,2,3,4,5. Furthermore, we do not fully understand how molecular structures of axonemes vary across motile-ciliated cell types in the body. Here we use cryoelectron microscopy, cryoelectron tomography and proteomics to resolve the 96-nm modular repeat of axonemal doublet microtubules (DMTs) from both sperm flagella and epithelial cilia of the oviduct, brain ventricles and respiratory tract. We find that sperm DMTs are the most specialized, with epithelial cilia having only minor differences across tissues. We build a model of the mammalian sperm DMT, defining the positions and interactions of 181proteins including 34newly identified proteins. We elucidate the composition of radial spoke3 and uncover binding sites of kinases associated with regeneration of ATP and regulation of ciliary motility. We discover a sperm-specific, axoneme-tethered T-complex protein ring complex (TRiC) chaperone that may contribute to construction or maintenance of the long flagella of mammalian sperm. We resolve axonemal dyneins in their prestroke states, illuminating conformational changes that occur during ciliary movement. Our results illustrate how elements of chemical and mechanical regulation are embedded within the axoneme, providing valuable resources for understanding the aetiology of ciliopathy and infertility, and exemplifying the discovery power of modern structural biology.

DOI: 10.1038/s41586-024-08337-5

Source: https://www.nature.com/articles/s41586-024-08337-5