Critical Determinants of the G Protein γ Subunits in the Gβγ Stimulation of G Protein-activated Inwardly Rectifying Potassium (GIRK) Channel Activity

Luying Peng, Tooraj Mirshahi, Hailin Zhang, Jeanne P. Hirsch, Diomedes E. Logothetis

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The βγ subunits of G proteins modulate inwardly rectifying potassium (GIRK) channels through direct interactions. Although GIRK currents are stimulated by mammalian Gβγ subunits, we show that they were inhibited by the yeast Gβγ (Ste4/Ste18) subunits. A chimera between the yeast and the mammalian Gβ1 subunits (ymβ) stimulated or inhibited GIRK currents, depending on whether it was co-expressed with mammalian or yeast Gγ subunits, respectively. This result underscores the critical functional influence of the Gγ subunits on the effectiveness of the Gβγ complex. A series of chimeras between Gγ2 and the yeast Gγ revealed that the C-terminal half of the Gγ 2 subunit is required for channel activation by the Gβγ complex. Point mutations of Gγ2 to the corresponding yeast Gγ residues identified several amino acids that reduced significantly the ability of Gβγ to stimulate channel activity, an effect that was not due to improper association with Gβ. Most of the identified critical Gγ residues clustered together, forming ah an intricate network of interactions with the Gβ subunit, defining an interaction surface of the Gβγ complex with GIRK channels. These results show for the first time a functional role for Gγ in the effector role of Gβγ.

Original languageEnglish
Pages (from-to)50203-50211
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number50
DOIs
StatePublished - 12 Dec 2003
Externally publishedYes

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