Molecular basis of egg coat cross-linking sheds light on ZP1-associated female infertility
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Authors
Nishimura, Kaoru
Dioguardi, Elisa
Nishio, Shunsuke
Villa, Alessandra
Han, Ling
Matsuda, Tsukasa
Jovine, Luca
Issue Date
2019-07-12
Type
Article
Language
en_US
Keywords
Glycoproteins , Oogenesis , X-ray Crystallography , Female Infertility
Alternative Title
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.
Description
Citation
Nishimura, K., Dioguardi, E., Nishio, S., Villa, A., Han, L., Matsuda, T., & Jovine, L. (2019). Molecular basis of egg coat cross-linking sheds light on ZP1-associated female infertility. Nature communications, 10(1), 3086. https://doi.org/10.1038/s41467-019-10931-5
Publisher
Nature Communications