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Abstract：
Mammalian fertilisation begins when sperm interacts with the egg zona pellucida (ZP), whose ZP1 subunit is important for fertility by covalently cross-linking ZP filaments into a three-dimensional matrix. Like ZP4, a structurally-related component absent in the mouse, ZP1 is predicted to contain an N-terminal ZP-N domain of unknown function. Here we report a characterisation of ZP1 proteins carrying mutations from infertile patients, which suggests that, in human, filament cross-linking by ZP1 is crucial to form a stable ZP. We map the function of ZP1 to its ZP-N1 domain and determine crystal structures of ZP-N1 homodimers from a chicken homolog of ZP1. These reveal that ZP filament cross-linking is highly plastic and can be modulated by ZP1 fucosylation and, potentially, zinc sparks. Moreover, we show that ZP4 ZP-N1 forms non-covalent homodimers in chicken but not in human. Together, these data identify human ZP1 cross-links as a promising target for non-hormonal contraception.
摘要：
当精子与卵透明带（ZP）相互作用时，哺乳动物受精开始，其ZP1亚基通过将ZP丝共价交联成三维基质对育性很重要。像ZP4，一个结构相关的组件在鼠标中不存在，预测ZP1包含功能未知的N末端ZP-N域。在这里，我们报告了携带不育患者突变的ZP1蛋白的特征，这表明，在人类中，通过ZP1的长丝交联对于形成稳定的ZP至关重要。我们将ZP1的功能映射到其ZP-N1结构域，并从ZP1的鸡同源物中确定ZP-N1同源二聚体的晶体结构。这些表明ZP长丝交联是高度塑性的，可以通过ZP1岩藻糖基化进行调节，潜在的,锌火花。此外，我们显示ZP4ZP-N1在鸡中形成非共价同源二聚体，而在人中不形成。一起,这些数据表明人类ZP1交联是非激素避孕的有希望的目标.
