| RRC ID |
39789
|
| 著者 |
Kato K, Satouh Y, Nishimasu H, Kurabayashi A, Morita J, Fujihara Y, Oji A, Ishitani R, Ikawa M, Nureki O.
|
| タイトル |
Structural and functional insights into IZUMO1 recognition by JUNO in mammalian fertilization.
|
| ジャーナル |
Nat Commun
|
| Abstract |
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.
|
| 巻・号 |
7
|
| ページ |
12198
|
| 公開日 |
2016-7-15
|
| DOI |
10.1038/ncomms12198
|
| PII |
ncomms12198
|
| PMID |
27416963
|
| PMC |
PMC4947182
|
| MeSH |
Animals
Binding Sites
Carrier Proteins / genetics
Carrier Proteins / metabolism
Cell Adhesion
Crystallography, X-Ray
Egg Proteins
Female
Fertilization / physiology*
Folate Receptor 1 / chemistry
Folate Receptor 1 / metabolism
HEK293 Cells
Humans
Immunoglobulins / chemistry
Immunoglobulins / genetics
Immunoglobulins / metabolism*
Male
Membrane Proteins / chemistry
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Mice, Knockout
Mutation
Receptors, Cell Surface / chemistry*
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism*
Sperm-Ovum Interactions / physiology
Tryptophan / genetics
Tryptophan / metabolism
|
| IF |
12.121
|
| 引用数 |
14
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
EGR-G101(AES0182) |
