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

B. Alexander Yi, Yu-Fung Lin, Yuh Nung Jan, Lily Yeh Jan

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)657-667
Number of pages11
JournalNeuron
Volume29
Issue number3
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Neuroscience(all)

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