Structural and functional insights into IZUMO1 recognition by JUNO in mammalian fertilization.
Structural and functional insights into IZUMO1 recognition by JUNO in mammalian fertilization.
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DOI：
10.1038/ncomms12198
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发表时间：
2016-07-15
影响因子：
16.6
通讯作者：
Nureki O
中科院分区：
文献类型：
--
作者：
Kato K;Satouh Y;Nishimasu H;Kurabayashi A;Morita J;Fujihara Y;Oji A;Ishitani R;Ikawa M;Nureki O
精卵融合是哺乳动物受精的关键步骤，需要精子表面的IZUMO1与卵子表面的JUNO（也称为叶酸受体（FR） 4或IZUMO1R）相互作用。虽然其他fr结合并摄取叶酸，但JUNO结合IZUMO1并建立细胞-细胞粘附。然而，朱诺识别IZUMO1的机制仍然难以捉摸。这里我们报道了鼠标JUNO的晶体结构，分辨率为2.3 Å。JUNO与FRs的结构比较显示JUNO与FRs具有相似的总体结构，但JUNO缺少叶酸结合袋，从而解释了JUNO无法结合叶酸的原因。将Juno基因敲除的卵子与突变的Juno信使rna进一步互补，发现Juno基因保守的、表面暴露的色氨酸残基是精子结合和受精所必需的。我们基于结构的体内功能分析为哺乳动物配子识别的机制理解提供了一个框架。精卵融合需要精子上的IZUMO1和卵子上的JUNO相互作用。在这里，作者报告了小鼠JUNO的晶体结构，并用它来解释它与叶酸缺乏结合的原因，并进行了体内功能分析。
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. Sperm-egg fusion requires the interaction between IZUMO1 on the sperm and JUNO on the egg. Here, the authors report the crystal structure of mouse JUNO, and use it to explain its lack of binding to folate, along with in vivo functional analyses.