期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-10931-5
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资金
- Karolinska Institutet
- Center for Biosciences
- Center for Innovative Medicine
- Swedish Research Council [2012-5093, 2016-03999]
- Goran Gustafsson Foundation for Research in Natural Sciences and Medicine
- Sven and Ebba-Christina Hagberg foundation
- EMBO Young Investigator award
- European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant [260759]
- JSPS KAKENHI grants [22112510, 17380200]
- Vinnova [2016-03999] Funding Source: Vinnova
- Swedish Research Council [2016-03999] Funding Source: Swedish Research Council
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.
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