Binding of the G protein βγ subunit to multiple regions of G protein-gated inward-rectifying K+ channels

Chou Long Huang, Yuh Nung Jan, Lily Y. Jan

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

We have previously shown that direct binding of the βγ subunit of G protein (Gβγ) to both the N-terminal domain and the C-terminal domain of a cloned G protein-gated inward rectifying K+ channel subunit, GIRK1, is important for channel activation. We have now further localized the Gβγ binding region in the N-terminal domain of GIRK1 to amino acids 34-86 and the Gβγ binding region in the C-terminal domain of GIRK1 to two separate fragments of amino acids 318-374 and amino acids 390-462. Of the four cloned mammalian GIRK subunits, GIRK1-4, GIRK1 and 4 form heteromeric K+ channels in the heart and similar channels in the brain include heteromultimers of GIRK1 and 2, and possibly other GLRK homomultimers and heteromultimers. We found that the N-terminal and the C-terminal domains of all four GIRKs bound Gβγ. The Gβγ binding activities for the C-terminal domains of GIRK2-4 were lower than that for the C-terminal domain of GIRK1. The higher Gβγ binding activity for the C-terminal domain of GIRK1 is due to amino acids 390-462 which are unique to GIRK1. We also found that the N-terminal and C-terminal domains of GIRKs interacted with each other, and the N-terminal domain of either GIRK1 or GIRK4 together with the C-terminal domain of GIRK1 exhibited much enhanced binding of Gβγ. These results are consistent with the idea that the N- and C-terminal domains of the cardiac G protein-gated K+ channel subunits may interact with each other to form higher affinity binding site(s) for Gβγ.

Original languageEnglish (US)
Pages (from-to)291-298
Number of pages8
JournalFEBS Letters
Volume405
Issue number3
DOIs
StatePublished - Apr 1 1997

Keywords

  • Direct protein-protein interaction
  • Fusion protein
  • G-protein-gated inwardly rectifying K channel
  • Glutathione-S-transferase
  • Gβγ binding
  • Weaver mutation

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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