期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms12198
关键词
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资金
- Core Research for Evolutional Science and Technology (CREST) Program, The Creation of Basic Chronic Inflammation, from Japan Science and Technology Agency (JST)
- KAKENHI [25112007, 25250014]
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [16H06294, 15H05573, 15J08403, 15J04519, 25112007, 25250014, 16H06276] Funding Source: KAKEN
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 angstrom 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-ased in vivo functional analyses provide a framework towards a mechanistic understanding of mammalian gamete recognition.
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