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

Matthew Whorton, Roderick MacKinnon

Research output: Contribution to journalArticle

244 Citations (Scopus)

Abstract

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
JournalCell
Volume147
Issue number1
DOIs
StatePublished - Sep 30 2011
Externally publishedYes

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GTP-Binding Proteins
Crystal structure
Sodium
Physiology
Heart Rate
Binding Sites
Ions
protein K

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Crystal structure of the mammalian GIRK2 K + channel and gating regulation by G proteins, PIP 2, and sodium. / Whorton, Matthew; MacKinnon, Roderick.

In: Cell, Vol. 147, No. 1, 30.09.2011, p. 199-208.

Research output: Contribution to journalArticle

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