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Molecular basis of egg coat cross-linking sheds light on ZP1-associated female infertility

Author

Listed:
  • Kaoru Nishimura

    (Karolinska Institutet)

  • Elisa Dioguardi

    (Karolinska Institutet)

  • Shunsuke Nishio

    (Nagoya University
    Karolinska Institutet)

  • Alessandra Villa

    (Karolinska Institutet)

  • Ling Han

    (Karolinska Institutet)

  • Tsukasa Matsuda

    (Nagoya University)

  • Luca Jovine

    (Karolinska Institutet)

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.

Suggested Citation

  • Kaoru Nishimura & Elisa Dioguardi & Shunsuke Nishio & Alessandra Villa & Ling Han & Tsukasa Matsuda & Luca Jovine, 2019. "Molecular basis of egg coat cross-linking sheds light on ZP1-associated female infertility," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10931-5
    DOI: 10.1038/s41467-019-10931-5
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