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A small region in phosducin inhibits G‐protein βγ‐subunit function
Author(s) -
Blüml Klaus,
Schnepp Werner,
Schröder Stefan,
Beyermann Michael,
Macias Maria,
Oschkinat Hartmut,
Lohse Martin J.
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.16.4908
Subject(s) - biology , g protein , heterotrimeric g protein , g alpha subunit , protein subunit , biochemistry , mastoparan , gtp binding protein regulators , gtpase activating protein , microbiology and biotechnology , signal transduction , gene
G‐protein βγ‐subunits (G βγ ) 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 βγ . Corresponding peptides not only disrupt G βγ –G α interactions, as defined by G βγ ‐stimulated GTPase activity of α o , but also other G βγ ‐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 βγ inhibitor, and illustrates the potential of small compounds to affect G βγ functions.