| RRC ID |
54929
|
| 著者 |
Miyagawa T, Koteishi H, Kamimura Y, Miyanaga Y, Takeshita K, Nakagawa A, Ueda M.
|
| タイトル |
Structural basis of Gip1 for cytosolic sequestration of G protein in wide-range chemotaxis.
|
| ジャーナル |
Nat Commun
|
| Abstract |
G protein interacting protein 1 (Gip1) binds and sequesters heterotrimeric G proteins in the cytosolic pool, thus regulating G protein-coupled receptor (GPCR) signalling for eukaryotic chemotaxis. Here, we report the underlying structural basis of Gip1 function. The crystal structure reveals that the region of Gip1 that binds to the G protein has a cylinder-like fold with a central hydrophobic cavity composed of six α-helices. Mutagenesis and biochemical analyses indicate that the hydrophobic cavity and the hydrogen bond network at the entrance of the cavity are essential for complex formation with the geranylgeranyl modification on the Gγ subunit. Mutations of the cavity impair G protein sequestration and translocation to the membrane from the cytosol upon receptor stimulation, leading to defects in chemotaxis at higher chemoattractant concentrations. These results demonstrate that the Gip1-dependent regulation of G protein shuttling ensures wide-range gradient sensing in eukaryotic chemotaxis.
|
| 巻・号 |
9(1)
|
| ページ |
4635
|
| 公開日 |
2018-11-6
|
| DOI |
10.1038/s41467-018-07035-x
|
| PII |
10.1038/s41467-018-07035-x
|
| PMID |
30401901
|
| PMC |
PMC6219514
|
| MeSH |
Chemotactic Factors / chemistry
Chemotaxis / physiology*
Crystallography, X-Ray
Cytosol / metabolism*
Dictyostelium
Eukaryota
GTP-Binding Proteins / chemistry*
GTP-Binding Proteins / genetics
Heterotrimeric GTP-Binding Proteins / chemistry*
Hydrogen Bonding
Models, Molecular
Mutagenesis
Mutation
Protein Binding
Protein Conformation
Protein Interaction Domains and Motifs
Protein Phosphatase 1
Receptors, G-Protein-Coupled / chemistry*
Saccharomyces cerevisiae Proteins
Signal Transduction
|
| IF |
11.878
|
| 引用数 |
2
|
| リソース情報 |
| 細胞性粘菌 |
S90887 |
