Referenced in: none

Automatically associated channels: Kir2.1 , Kir3.1

Title: Structural basis for the modulation of the gating property of G protein-gated inwardly rectifying potassium ion channel (GIRK) by the i/o-family G protein α subunit (Gαi/o).

Authors: Yoko Mase, Mariko Yokogawa, Masanori Osawa, Ichio Shimada

Journal, date & volume: , 2012 Apr 16 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22511772

Abstract
G protein-gated inwardly rectifying potassium channel (GIRK) plays a crucial role in regulating heart rate and neuronal excitability. The gating of GIRK is regulated by the association and dissociation of G protein βγ subunits (Gβγ), which are released from pertussis toxin-sensitive G protein α subunit (Gα(i/o)) upon GPCR activation in vivo. Several lines of evidence indicate that Gα(i/o) also interacts directly with GIRK, playing functional roles in the signaling efficiency and the modulation of the channel activity. However, the underlying mechanism for GIRK regulation by Gα(i/o) remains to be elucidated. Here, we performed NMR analyses of the interaction between the cytoplasmic region of GIRK1 and Gα(i3) in the GTP-bound state. The NMR spectral changes of Gα upon the addition of GIRK as well as the transferred cross-saturation (TCS) results indicated their direct binding mode, where the K(d) value was estimated as ∼1 mm. The TCS experiments identified the direct binding sites on Gα and GIRK as the α2/α3 helices on the GTPase domain of Gα and the αA helix of GIRK. In addition, the TCS and paramagnetic relaxation enhancement results suggested that the helical domain of Gα transiently interacts with the αA helix of GIRK. Based on these results, we built a docking model of Gα and GIRK, suggesting the molecular basis for efficient GIRK deactivation by Gα(i/o).