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Neuron. 2001 Mar;29(3):657-67.

Yeast screen for constitutively active mutant G protein-activated potassium channels.

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Departments of Physiology and Biochemistry, Howard Hughes Medical Institute, University of California, San Francisco, 533 Parnassus Avenue, San Francisco, CA 94143, USA.


GIRK2 is a major contributor to G protein-activated inward rectifier potassium channels in the mammalian brain. How GIRK channels open upon contact with Gbetagamma 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.

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