GIRK2 is a major contributor to G protein-activated inward rectifier potassium channels in the mammalian brain. How GIRK channels open upon contact with Gβγ remains unknown. Using a yeast genetic screen to select constitutively active mutants from a randomly mutagenized GIRK2 library, we identified five gating mutations at four residues in the transmembrane domain. Further mutagenesis indicates that GIRK channel opening involves a rotation of the transmembrane segments, bringing one of these residues (V188) to a pore-lining position in the open conformation. Combined with double-mutant studies, these findings suggest that GIRK channels gate by moving from the open conformation inferred from our yeast study of Kir2.1 to a closed conformation perhaps resembling the known KcsA structure.
Yi, B. A., Lin, Y. F., Jan, Y. N., & Jan, L. Y. (2001). Yeast screen for constitutively active mutant G protein-activated potassium channels. Neuron, 29(3), 657–667. https://doi.org/10.1016/S0896-6273(01)00241-0