Identification of critical residues controlling G protein-gated inwardly rectifying K(+) channel activity through interactions with the beta gamma subunits of G proteins.

G protein-sensitive inwardly rectifying potassium (GIRK) channels are activated through direct interactions of their cytoplasmic N- and C-terminal domains with the beta gamma subunits of G proteins. By using a combination of biochemical and electrophysiological approaches, we identified minimal N- and C-terminal G beta gamma -binding domains responsible for stimulation ...
of GIRK4 channel activity. Within these domains one N-terminal residue, His-64, and one C-terminal residue, Leu-268, proved critical for G beta gamma-mediated GIRK4 activity. Moreover, mutations at these GIRK4 sites reduced significantly binding of the channel domains to G beta gamma . The corresponding residues in GIRK1 also showed a critical involvement in G beta gamma sensitivity. In GIRK4/GIRK1 heteromers the GIRK4 His-64 and Leu-268 residues showed greater contributions to G beta zeta sensitivity than did the corresponding GIRK1 His-57 and Leu-262 residues. These results identify functionally important channel interaction sites with the beta gamma subunits of G proteins, critical for channel activity.
Mesh Terms:
Amino Acid Sequence, Animals, Binding Sites, Cattle, G Protein-Coupled Inwardly-Rectifying Potassium Channels, GTP-Binding Proteins, Leucine, Molecular Sequence Data, Mutagenesis, Site-Directed, Peptide Fragments, Potassium Channels, Potassium Channels, Inwardly Rectifying, Protein Subunits, Recombinant Fusion Proteins, Recombinant Proteins
J. Biol. Chem.
Date: Feb. 22, 2002
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