中国科学院生物物理研究所孙飞小组的一项最新研究报道了小鼠精子中心装置的原位结构揭示了弱精子症的机制。该项研究成果发表在2025年6月5日出版的《细胞研究》上。

结合冷冻电子断层扫描和AlphaFold2，该课题组研究人员在亚纳米分辨率下解析了单主题精子CA的细胞内结构，并建立了一个接近完整的原子模型。他们的分析确定了39种CA相关蛋白，包括8种以前未报道的成分。通过展示CFAP47和HYDIN的全长结构，研究团队阐明了它们在CA内拴住C1和C2微管中的分子作用。具体来说，HYDIN形成了一个围绕C1和C2的半圆形链，其N端一半驱动C1 - C2连接，C端一半在C2中提供轴向支撑。CFAP47是该桥的核心结构成分，通过其N端结构域结合C1，通过其中心CFAP47环与HYDIN相互作用，并通过其C端区域锚定到C2。在CFAP47敲除小鼠中观察到的精子活力显著降低和CA结构受损证实了CFAP47的重要作用。

此外，对患有弱精子症的不育中国男性的遗传分析发现了以前未报道的CFAP47突变。CA结构模型阐明了这些突变的致病机制，建立了CFAP47功能障碍与精子活力受损之间的直接联系。因此，他们的研究为CA相关的生育障碍提供了机制见解。

据介绍，精子轴素中的中央装置（CA）对精子的运动至关重要，但其分子结构和功能机制仍未完全了解。

附：英文原文

Title: In situ structure of the mouse sperm central apparatus reveals mechanistic insights into asthenozoospermia

Author: Zhu, Yun, Lin, Tingting, Yin, Guoliang, Tai, Linhua, Chen, Lianwan, Ma, Jing, Huang, Guoning, Lu, Yi, Zhang, Zhiyong, Wang, Binbin, Chen, Suren, Sun, Fei

Issue&Volume: 2025-06-05

Abstract: The central apparatus (CA) within the sperm axoneme is vital for sperm motility, yet its molecular architecture and functional mechanisms remain incompletely understood. Combining cryo-electron tomography and AlphaFold2, we resolved the in-cell structure of mouse sperm CA at a subnanometer resolution and built a near-complete atomic model. Our analysis identified 39 CA-associated proteins, including eight previously unreported components. By presenting the full-length structures of CFAP47 and HYDIN, we elucidate their molecular roles in tethering the C1 and C2 microtubules within the CA. Specifically, HYDIN forms a semicircular chain that encircles C1 and C2, with its N-terminal half driving the C1–C2 connection and its C-terminal half providing axial support in C2. CFAP47, the core structural component of the bridge, binds C1 through its N-terminal domains, interacts with HYDIN via its central CFAP47-ring, and anchors to C2 through its C-terminal region. The significantly reduced sperm motility and impaired CA structure observed in Cfap47-knockout mice confirmed the important role of CFAP47. Furthermore, genetic analysis of infertile Chinese men with asthenozoospermia identified previously unreported mutations in the CFAP47. The CA structural model elucidates the pathogenic mechanisms of these mutations, establishing a direct link between CFAP47 dysfunction and impaired sperm motility. Therefore, our study provides mechanistic insights into CA-related fertility disorders.

DOI: 10.1038/s41422-025-01135-2

Source: https://www.nature.com/articles/s41422-025-01135-2