Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Nat Struct Mol Biol. 2023 Mar;30(3):360-369. doi: 10.1038/s41594-022-00861-0. Epub 2023 Jan 2.
The flagella of mammalian sperm display non-planar, asymmetric beating, in contrast to the planar, symmetric beating of flagella from sea urchin sperm and unicellular organisms. The molecular basis of this difference is unclear. Here, we perform in situ cryo-electron tomography of mouse and human sperm, providing the highest-resolution structural information to date. Our subtomogram averages reveal mammalian sperm-specific protein complexes within the microtubules, the radial spokes and nexin-dynein regulatory complexes. The locations and structures of these complexes suggest potential roles in enhancing the mechanical strength of mammalian sperm axonemes and regulating dynein-based axonemal bending. Intriguingly, we find that each of the nine outer microtubule doublets is decorated with a distinct combination of sperm-specific complexes. We propose that this asymmetric distribution of proteins differentially regulates the sliding of each microtubule doublet and may underlie the asymmetric beating of mammalian sperm.
哺乳动物精子的鞭毛呈现出非平面、不对称的运动方式，与海胆精子和单细胞生物的平面、对称的运动方式形成对比。这种差异的分子基础尚不清楚。在这里，我们对小鼠和人类精子进行了原位冷冻电子断层扫描，提供了迄今为止最高分辨率的结构信息。我们的亚断层平均显示了微管内、辐条和连接蛋白-动力蛋白调节复合物中的哺乳动物精子特异性蛋白复合物。这些复合物的位置和结构表明它们可能在增强哺乳动物精子轴丝的机械强度和调节基于动力蛋白的轴丝弯曲方面发挥作用。有趣的是，我们发现九个外部微管二联体中的每一个都被独特组合的精子特异性复合物所装饰。我们提出，这种蛋白质的不对称分布差异调节了每个微管二联体的滑动，可能是哺乳动物精子不对称运动的基础。
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