PMID: 27416963

 

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

Abstract :

1. 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
2. Whereas other FRs bind and uptake folates, JUNO binds IZUMO1 and establishes the cell-cell adhesion
3. However, the mechanism of IZUMO1 recognition by JUNO has remained elusive
4. Here we report the crystal structure of mouse JUNO , at 2.3 Å resolution
5. 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
6. 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
7. Our structure-based in vivo functional analyses provide a framework towards a mechanistic understanding of mammalian gamete recognition