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

Mol Cell. 1999 May;3(5):649-60. doi: 10.1016/s1097-2765(00)80358-5.

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 (Gt alpha beta gamma) available through sequestration of the beta gamma subunits (Gt beta gamma). The structure of the phosphophosducin/Gt beta gamma complex combined with mutational and biophysical analysis provides a stereochemical mechanism for the regulation of the phosducin-Gt beta gamma 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 Gt beta gamma, leading to the release of unencumbered Gt beta gamma, which reassociates with the membrane and Gt alpha to form a signaling-competent Gt alpha beta gamma heterotrimer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Circular Dichroism
  • DNA Mutational Analysis
  • Endopeptidases / metabolism
  • Eye Proteins / chemistry
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • GTP-Binding Protein Regulators
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / metabolism*
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Mutagenesis / physiology
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Kinases / metabolism
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Rats
  • Rhodopsin / metabolism
  • Serine
  • Vision, Ocular / physiology*

Substances

  • Eye Proteins
  • GTP-Binding Protein Regulators
  • Phosphoproteins
  • phosducin
  • Serine
  • Rhodopsin
  • Protein Kinases
  • Endopeptidases
  • GTP-Binding Proteins

Associated data

  • PDB/1B9X
  • PDB/1B9Y