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PMID: 9305633 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A small region in phosducin inhibits G-protein betagamma-subunit function.

The EMBO journal ·Vol. 16 ·No. 16 ·1997-08-15 ·Pages 4908-15

Blüml K, Schnepp W, Schröder S, Beyermann M, Macias M, Oschkinat H, Lohse MJ

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.

MeSH Terms
Amino Acid Sequence Animals Blotting, Western Cattle Crystallography, X-Ray Eye Proteins/chemistry,genetics,metabolism,pharmacology GTP Phosphohydrolases/antagonists & inhibitors,metabolism GTP-Binding Protein Regulators GTP-Binding Proteins/antagonists & inhibitors,metabolism Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Mutation Peptide Fragments/chemistry,metabolism,pharmacology Phosphoproteins/chemistry,genetics,metabolism,pharmacology Protein Binding Protein Kinases/genetics,metabolism Protein Structure, Secondary Recombinant Fusion Proteins/chemistry,metabolism,pharmacology
Chemicals
Eye Proteins GTP-Binding Protein Regulators Peptide Fragments Phosphoproteins Recombinant Fusion Proteins phosducin Protein Kinases GTP Phosphohydrolases GTP-Binding Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Blüml K
Institut für Pharmakologie und Toxikologie der Universität Würzburg, Germany.
Schnepp W
Schröder S
Beyermann M
Macias M
Oschkinat H
Lohse M J
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/16.16.4908
Published
1997-08-15
Pages
4908-15
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170126
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/16.16.4908 PMC Full Text View journal details
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