Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium

Matthew R. Whorton, Roderick MacKinnon

Research output: Contribution to journalArticlepeer-review

324 Scopus citations

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 PIP2, but in the presence of PIP2 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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium'. Together they form a unique fingerprint.

Cite this