A small region in phosducin inhibits G-protein betagamma-subunit function
- PMID: 9305633
- PMCID: PMC1170126
- DOI: 10.1093/emboj/16.16.4908
A small region in phosducin inhibits G-protein betagamma-subunit function
Abstract
G-protein betagamma-subunits (G(betagamma)) are active transmembrane signalling components. Their function recently has been observed to be regulated by the cytosolic protein phosducin. We show here that a small fragment (amino acids 215-232) contained in the C-terminus of phosducin is sufficient for high-affinity interactions with G(betagamma). Corresponding peptides not only disrupt G(betagamma)-G(alpha) interactions, as defined by G(betagamma)-stimulated GTPase activity of alpha(o), but also other G(betagamma)-mediated functions. The NMR structure of a peptide encompassing this region shows a loop exposing the side chains of Glu223 and Tyr224, and peptides with a substitution of either of these amino acids show a complete loss of activity towards G(o). Mutation of this Tyr224 to Ala in full-length phosducin reduced the functional activity of phosducin to that of phosducin's isolated N-terminus, indicating the importance of this residue within the short, structurally defined C-terminal segment. This small peptide derived from phosducin, may represent a model of a G(betagamma) inhibitor, and illustrates the potential of small compounds to affect G(betagamma) functions.
Similar articles
-
Inhibition of G-protein betagamma-subunit functions by phosducin-like protein.Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2100-4. doi: 10.1073/pnas.93.5.2100. Proc Natl Acad Sci U S A. 1996. PMID: 8700891 Free PMC article.
-
Identification of a C-terminal binding site for G-protein betagamma-subunits in phosducin-like protein.FEBS Lett. 1997 Jan 20;401(2-3):243-6. doi: 10.1016/s0014-5793(96)01483-4. FEBS Lett. 1997. PMID: 9013896
-
Effects of phosducin on the GTPase cycle of Go.Naunyn Schmiedebergs Arch Pharmacol. 1998 Apr;357(4):371-7. doi: 10.1007/pl00005181. Naunyn Schmiedebergs Arch Pharmacol. 1998. PMID: 9606021
-
The pharmacology of phosducin.Pharmacol Res. 2001 Jan;43(1):1-10. doi: 10.1006/phrs.2000.0757. Pharmacol Res. 2001. PMID: 11207059 Review.
-
The physiological roles of phosducin: from retinal function to stress-dependent hypertension.Cell Mol Life Sci. 2011 Feb;68(4):599-612. doi: 10.1007/s00018-010-0550-0. Epub 2010 Oct 31. Cell Mol Life Sci. 2011. PMID: 21069424 Free PMC article. Review.
Cited by
-
Phosducin-like proteins in Dictyostelium discoideum: implications for the phosducin family of proteins.EMBO J. 2003 Oct 1;22(19):5047-57. doi: 10.1093/emboj/cdg508. EMBO J. 2003. PMID: 14517243 Free PMC article.
-
Phosducin regulates transmission at the photoreceptor-to-ON-bipolar cell synapse.J Neurosci. 2010 Mar 3;30(9):3239-53. doi: 10.1523/JNEUROSCI.4775-09.2010. J Neurosci. 2010. PMID: 20203183 Free PMC article.
-
Structural features of heterotrimeric G-protein-coupled receptors and their modulatory proteins.Mol Neurobiol. 1999 Apr;19(2):111-49. doi: 10.1007/BF02743657. Mol Neurobiol. 1999. PMID: 10371466 Review.
-
Identification of bdm-1, a gene involved in G protein beta-subunit function and alpha-subunit accumulation.Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):412-7. doi: 10.1073/pnas.97.1.412. Proc Natl Acad Sci U S A. 2000. PMID: 10618432 Free PMC article.
-
Regulators of G-protein signalling in Fusarium verticillioides mediate differential host-pathogen responses on nonviable versus viable maize kernels.Mol Plant Pathol. 2011 Jun;12(5):479-91. doi: 10.1111/j.1364-3703.2010.00686.x. Epub 2011 Jan 7. Mol Plant Pathol. 2011. PMID: 21535353 Free PMC article.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources