Crystal structure of the mammalian GIRK2 K + channel and gating regulation by G proteins, PIP 2, and sodium

Matthew R. Whorton, Roderick MacKinnon

Research output: Contribution to journalArticle

262 Scopus citations


G protein-gated K + channels (Kir3.1-Kir3.4) control electrical excitability in many different cells. Among their functions relevant to human physiology and disease, they regulate the heart rate and govern a wide range of neuronal activities. Here, we present the first crystal structures of a G protein-gated K + channel. By comparing the wild-type structure to that of a constitutively active mutant, we identify a global conformational change through which G proteins could open a G loop gate in the cytoplasmic domain. The structures of both channels in the absence and presence of PIP 2 suggest that G proteins open only the G loop gate in the absence of PIP 2, but in the presence of PIP 2 the G loop gate and a second inner helix gate become coupled, so that both gates open. We also identify a strategically located Na + ion-binding site, which would allow intracellular Na + to modulate GIRK channel activity. These data provide a structural basis for understanding multiligand regulation of GIRK channel gating.

Original languageEnglish (US)
Pages (from-to)199-208
Number of pages10
Issue number1
StatePublished - Sep 30 2011


ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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