Editors' ChoiceG Proteins

Activation Without Dissociation

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Science's STKE  06 Jan 2004:
Vol. 2004, Issue 214, pp. tw2
DOI: 10.1126/stke.2142004tw2

Using fluorescence resonance energy transfer (FRET), Bünemann et al. observed that the heterotrimeric guanine nucleotide-binding proteins (G proteins) did not dissociate upon activation. This is contrary to the dogma that states that activation of the Gα subunit by binding of guanosine triphosphate causes dissociation of the α and βγ subunits. Fusion proteins between modified green fluorescent proteins and Gαi1 and Gβ1 or Gγ2 were expressed in human embryonic kidney cells. Surprisingly, the FRET signal detectable with either the labeled γ and α or β and α subunits increased upon stimulation of heterologously expressed adrenergic receptors. To confirm that the subunits underwent a rearrangement that caused the N termini of the γβ subunits to move closer to the αAB loop of Gαi, the authors constructed another fusion protein, cyan fluorescent protein attached to the C terminus of the Gγ2, that showed a decrease in FRET when stimulated. The functional coupling of the fluorescent fusion proteins was tested, and all except the C-terminally tagged γ subunit G proteins were able to stimulate the G protein-activated inwardly rectifying K+ channel. Thus, at least for Gi heterotrimers activated by α2-adrenergic receptors, G protein activation does not involve dissociation of the heterotrimer.

M. Bünemann, M. Frank, M. J. Lohse, Gi protein activation in intact cells involves subunit rearrangement rather than dissociation. Proc. Natl. Acad. Sci. U.S.A. 100, 16077-16082 (2003). [Abstract] [Full Text]

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