Medicine and Health Sciences Commons^™

A Computational Model Reveals The Action Of Gβγ At An Inter-Subunit Cleft To Activate Girk1 Channels, Rahul Mahajan, Junghoon Ha, Miao Zhang, Takeharu Kawano, Tohru Kozasa, Diomedes E. Logothetis

Pharmacy Faculty Articles and Research

The atrial G protein-regulated inwardly rectifying K+ (GIRK1 and GIRK4) heterotetrameric channels underlie the acetylcholine-induced K+ current responsible for vagal inhibition of heart rate and are activated by the G protein βγ subunits (Gβγ). We used a multistage protein-protein docking approach with data from published structures of GIRK1 and Gβγ to generate an experimentally testable interaction model of Gβγ docked onto the cytosolic domains of the GIRK1 homotetramer. The model suggested a mechanism by which Gβγ promotes the open state of a specific cytosolic gate in the channel, the G-loop gate. The predicted structure showed that the Gβ subunit interacts …