Structure of IZUMO1-JUNO reveals sperm-oocyte recognition during mammalian fertilization

被引：108

作者：

Ohto, Umeharu ^{[1
]}

Ishida, Hanako ^{[1
]}

Krayukhina, Elena ^{[2
]}

Uchiyama, Susumu ^{[2
,3
]}

Inoue, Naokazu ^{[4
]}

Shimizu, Toshiyuki ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan

[2] Osaka Univ, Grad Sch Engn, 2-1 Yamadaoka, Suita, Osaka 5650871, Japan

[3] Natl Inst Nat Sci, Okazaki Inst Integrat Biosci, 5-1 Higashiyama, Okazaki, Aichi 4448787, Japan

[4] Fukushima Med Univ, Sch Med, Inst Biomed Sci, Dept Cell Sci, 1 Hikarigaoka, Fukushima, Fukushima 9601295, Japan

来源：

NATURE | 2016年 / 534卷 / 7608期

关键词：

CRYSTAL-STRUCTURE; PROTEIN IZUMO; EGG FUSION; ULTRACENTRIFUGATION; FOLATE; JUNO;

D O I：

10.1038/nature18596

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Fertilization is a fundamental process in sexual reproduction, creating a new individual through the combination of male and female gametes(1-4). The IZUMO1 sperm membrane protein(5) and its counterpart oocyte receptor JUNO(6) have been identified as essential factors for sperm-oocyte interaction and fusion. However, the mechanism underlying their specific recognition remains poorly defined. Here, we show the crystal structures of human IZUMO1, JUNO and the IZUMO1-JUNO complex, establishing the structural basis for the IZUMO1-JUNO-mediated sperm-oocyte interaction. IZUMO1 exhibits an elongated rod-shaped structure comprised of a helical bundle IZUMO domain and an immunoglobulin-like domain that are each firmly anchored to an intervening beta-hairpin region through conserved disulfide bonds. The central beta-hairpin region of IZUMO1 provides the main platform for JUNO binding, while the surface located behind the putative JUNO ligand binding pocket is involved in IZUMO1 binding. Structure-based mutagenesis analysis confirms the biological importance of the IZUMO1-JUNO interaction. This structure provides a major step towards elucidating an essential phase of fertilization and it will contribute to the development of new therapeutic interventions for fertility, such as contraceptive agents.

引用

页码：566 / +

页数：16

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