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

Kazuki Kato, Yuhkoh Satouh, Hiroshi Nishimasu, Arisa Kurabayashi, Junko Morita, Yoshitaka Fujihara, Asami Oji, Ryuichiro Ishitani, Masahito Ikawa () and Osamu Nureki ()
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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
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

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: 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.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12198

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DOI: 10.1038/ncomms12198

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