Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nat Commun. 2016 Jul 15;7:12198. doi: 10.1038/ncomms12198.
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.
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 并建立细胞间黏附。然而，IZUMO1 被 JUNO 识别的机制仍然难以捉摸。在这里，我们报告了 2.3Å 分辨率的小鼠 JUNO 的晶体结构。JUNO 与 FRs 的结构比较表明，JUNO 和 FRs 具有相似的整体结构，但 JUNO 缺乏叶酸结合口袋，从而解释了 JUNO 不能结合叶酸的原因。用突变的 Juno mRNA 补充 Juno 敲除卵进一步表明，JUNO 表面暴露的保守色氨酸残基对于精子结合和受精是必需的。我们基于结构的体内功能分析为理解哺乳动物配子识别的机制提供了一个框架。
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