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Structural and functional insights into IZUMO1 recognition by JUNO in mammalian fertilization

Author

Listed:
  • Kazuki Kato

    (Graduate School of Science, The University of Tokyo)

  • Yuhkoh Satouh

    (Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka)

  • Hiroshi Nishimasu

    (Graduate School of Science, The University of Tokyo
    PRESTO, JST, 2-11-16 Yayoi)

  • Arisa Kurabayashi

    (Graduate School of Science, The University of Tokyo)

  • Junko Morita

    (Graduate School of Science, The University of Tokyo)

  • Yoshitaka Fujihara

    (Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka)

  • Asami Oji

    (Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka)

  • Ryuichiro Ishitani

    (Graduate School of Science, The University of Tokyo)

  • Masahito Ikawa

    (Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka)

  • Osamu Nureki

    (Graduate School of Science, The University of Tokyo)

Abstract

Sperm–egg fusion is the critical step in mammalian fertilization, and requires the interaction between IZUMO1 on the sperm surface and JUNO (also known as folate receptor (FR) 4 or IZUMO1R) on the egg surface. Whereas other FRs bind and uptake folates, JUNO binds IZUMO1 and establishes the cell–cell adhesion. However, the mechanism of IZUMO1 recognition by JUNO has remained elusive. Here we report the crystal structure of mouse JUNO, at 2.3 Å resolution. A structural comparison of JUNO with the FRs revealed that JUNO and the FRs have similar overall structures, but JUNO lacks the folate-binding pocket, thereby explaining the inability of JUNO to bind folate. Further complementation of Juno knockout eggs with mutant Juno messenger RNAs revealed that the conserved, surface-exposed tryptophan residue of JUNO is required for sperm binding and fertilization. Our structure-based in vivo functional analyses provide a framework towards a mechanistic understanding of mammalian gamete recognition.

Suggested Citation

  • Kazuki Kato & Yuhkoh Satouh & Hiroshi Nishimasu & Arisa Kurabayashi & Junko Morita & Yoshitaka Fujihara & Asami Oji & Ryuichiro Ishitani & Masahito Ikawa & Osamu Nureki, 2016. "Structural and functional insights into IZUMO1 recognition by JUNO in mammalian fertilization," Nature Communications, Nature, vol. 7(1), pages 1-9, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12198
    DOI: 10.1038/ncomms12198
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