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.

中文翻译：

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一种保守的受精复合物在脊椎动物中桥接精子和卵子


受精是有性繁殖的基础，最终以精子和卵子的结合和融合而告终。尽管已知几种蛋白质对脊椎动物的这一过程至关重要，但其分子机制仍然知之甚少。使用 AlphaFold-Multimer 筛选，我们鉴定出蛋白质 Tmem81 是具有必需受精因子 Izumo1 和 Spaca6 的保守三聚体精子复合物的一部分。我们证明 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，我们表明 Izumo1、Spaca6 和 Tmem81 在斑马鱼精子中相互作用，并且人类直系同源物在 体外相互作用。值得注意的是，复合物的形成为斑马鱼中的卵子受精因子 Bouncer 创造了结合位点。总之，我们的工作提出了一个跨脊椎动物受精的综合模型，其中保守的精子复合物与不同的卵子蛋白（鱼类中的 Bouncer 和哺乳动物中的 JUNO）结合以介导精子-卵子相互作用。