Digital Commons Network^™

Gβγ Acts At An Inter-Subunit Cleft To Activate Girk1 Channels, Rahul Mahajan

Theses and Dissertations

Heterotrimeric guanine nucleotide-binding proteins (G-proteins) consist of an alpha subunit (Gα) and the dimeric beta-gamma subunit (Gβγ). The first example of direct cell signaling by Gβγ was the discovery of its role in activating G-protein regulated inwardly rectifying K+ (GIRK) channels which underlie the acetylcholine-induced K+ current responsible for vagal inhibition of heart rate. Published crystal structures have provided important insights into the structures of the G-protein subunits and GIRK channels separately, but co-crystals of the channel and Gβγ together remain elusive and no specific reciprocal residue interactions between the two proteins are currently known. Given the absence of direct …