2024年10月17日，《细胞》杂志在线发表了奥地利科学家的一项最新研究成果。来自奥地利分子病理研究所的Andrea Pauli等研究人员合作发现，一个保守的受精复合体脊椎动物中连接精子与卵细胞。

通过AlphaFold-Multimer筛选，研究人员识别了蛋白质Tmem81，作为与必需的受精因子Izumo1和Spaca6组成的保守三聚体精子复合体的一部分。研究人员证明Tmem81对斑马鱼和小鼠的雄性生育能力至关重要。

与三聚体形成一致，研究人员展示了Izumo1、Spaca6和Tmem81在斑马鱼精子中相互作用，并且人类同源物在体外相互作用。值得注意的是，复合体的形成为斑马鱼的卵子受精因子Bouncer创造了结合位点。

总的来说，该研究提供了一个全面的脊椎动物受精模型，其中保守的精子复合体与不同的卵子蛋白结合——即鱼类中的Bouncer和哺乳动物中的JUNO，以介导精子与卵子的相互作用。

据悉，受精是性繁殖的基础，最终导致精子和卵子的结合与融合。虽然已知几种蛋白质对这一过程在脊椎动物中至关重要，但分子机制仍不清楚。

附：英文原文

Title: A conserved fertilization complex bridges sperm and egg in vertebrates

Author: Victoria E. Deneke, Andreas Blaha, Yonggang Lu, Johannes P. Suwita, Jonne M. Draper, Clara S. Phan, Karin Panser, Alexander Schleiffer, Laurine Jacob, Theresa Humer, Karel Stejskal, Gabriela Krssakova, Elisabeth Roitinger, Dominik Handler, Maki Kamoshita, Tyler D.R. Vance, Xinyin Wang, Joachim M. Surm, Yehu Moran, Jeffrey E. Lee, Masahito Ikawa, Andrea Pauli

Issue&Volume: 2024-10-17

Abstract: Fertilization, the basis for sexual reproduction, culminates in the binding and fusion of sperm and egg. Although several proteins are known to be crucial for this process in vertebrates, the molecular mechanisms remain poorly understood. Using an AlphaFold-Multimer screen, we identified the protein Tmem81 as part of a conserved trimeric sperm complex with the essential fertilization factors Izumo1 and Spaca6. We demonstrate that Tmem81 is essential for male fertility in zebrafish and mice. In line with trimer formation, we show that Izumo1, Spaca6, and Tmem81 interact in zebrafish sperm and that the human orthologs interact in vitro. Notably, complex formation creates the binding site for the egg fertilization factor Bouncer in zebrafish. Together, our work presents a comprehensive model for fertilization across vertebrates, where a conserved sperm complex binds to divergent egg proteins—Bouncer in fish and JUNO in mammals—to mediate sperm-egg interaction.

DOI: 10.1016/j.cell.2024.09.035

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01093-6