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. 1997 Aug 15;16(16):4908–4915. doi: 10.1093/emboj/16.16.4908

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

K Blüml 1, W Schnepp 1, S Schröder 1, M Beyermann 1, M Macias 1, H Oschkinat 1, M J Lohse 1
PMCID: PMC1170126  PMID: 9305633

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.

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Selected References

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