A molecular mechanism for the phosphorylation-dependent regulation of heterotrimeric G proteins by phosducin

Rachelle Gaudet, Justin R. Savage, Joseph N. McLaughlin, Barry M. Willardson, Paul B. Sigler

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Visual signal transduction is a nearly noise-free process that is exquisitely well regulated over a wide dynamic range of light intensity. A key component in dark/light adaptation is phosducin, a phosphorylatable protein that modulates the amount of transducin heterotrimer (G(t)αβγ) available through sequestration of the βγ subunits (G(t)βγ). The structure of the phosphophosducin/G(t)βγ complex combined with mutational and biophysical analysis provides a stereochemical mechanism for the regulation of the phosducin-G(t)βγ interaction. Phosphorylation of serine 73 causes an order-to-disorder transition of a 20-residue stretch, including the phosphorylation site, by disrupting a helix-capping motif. This transition disrupts phosducin's interface with G(t)βγ, leading to the release of unencumbered G(t)βγ, which reassociates with the membrane and G(t)α to form a signaling-competent G(t)αβγ heterotrimer.

Original languageEnglish (US)
Pages (from-to)649-660
Number of pages12
JournalMolecular cell
Volume3
Issue number5
DOIs
Publication statusPublished - Jan 1 1999
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this