| RRC ID |
46671
|
| Author |
Porter MY, Xie K, Pozharski E, Koelle MR, Martemyanov KA.
|
| Title |
A conserved protein interaction interface on the type 5 G protein beta subunit controls proteolytic stability and activity of R7 family regulator of G protein signaling proteins.
|
| Journal |
J Biol Chem
|
| Abstract |
Regulators of G protein signaling (RGS) proteins of the R7 subfamily limit signaling by neurotransmitters in the brain and by light in the retina. They form obligate complexes with the Gβ5 protein that are subject to proteolysis to control their abundance and alter signaling. The mechanisms that regulate this proteolysis, however, remain unclear. We used genetic screens to find mutations in Gβ5 that selectively destabilize one of the R7 RGS proteins in Caenorhabditis elegans. These mutations cluster at the binding interface between Gβ5 and the N terminus of R7 RGS proteins. Equivalent mutations within mammalian Gβ5 allowed the interface to still bind the N-terminal DEP domain of R7 RGS proteins, and mutant Gβ5-R7 RGS complexes initially formed in cells but were then rapidly degraded by proteolysis. Molecular dynamics simulations suggest the mutations weaken the Gβ5-DEP interface, thus promoting dynamic opening of the complex to expose determinants of proteolysis known to exist on the DEP domain. We propose that conformational rearrangements at the Gβ5-DEP interface are key to controlling the stability of R7 RGS protein complexes.
|
| Volume |
285(52)
|
| Pages |
41100-12
|
| Published |
2010-12-24
|
| DOI |
10.1074/jbc.M110.163600
|
| PII |
S0021-9258(19)76276-0
|
| PMID |
20959458
|
| PMC |
PMC3003408
|
| MeSH |
Animals
Caenorhabditis elegans / chemistry*
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins / chemistry*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism
Computer Simulation*
GTP-Binding Protein beta Subunits / chemistry*
GTP-Binding Protein beta Subunits / genetics
GTP-Binding Protein beta Subunits / metabolism
HEK293 Cells
Humans
Models, Molecular*
Multiprotein Complexes
Mutation
Protein Binding
Protein Structure, Quaternary
Protein Structure, Tertiary
RGS Proteins / chemistry*
RGS Proteins / genetics
RGS Proteins / metabolism
|
| IF |
4.238
|
| Times Cited |
13
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| C.elegans |
tm761 |
