Lipid modification at the N terminus of photoreceptor G-protein alpha-subunit

Nature. 1992 Oct 22;359(6397):749-52. doi: 10.1038/359749a0.

Abstract

Myristate is a fatty acid (fourteen-carbon chain with no double bonds, C14:0) linked to the amino-terminal glycine of several proteins, including alpha-subunits of heterotrimeric (alpha/beta gamma) G proteins. We report here a novel modification at the N terminus of the alpha-subunit of the photoreceptor G protein transducin, T alpha, with heterogeneous fatty acids composed of laurate (C12:0), unsaturated C14:2 and C14:1 fatty acids, and a small amount (approximately 5%) of myristate. Both the GTPase activity of T alpha/T beta gamma and the T beta gamma-dependent ADP-ribosylation of T alpha catalysed by pertussis toxin were inhibited by the lauroylated and myristoylated N-terminal peptide of T alpha. The myristoylated peptide gave 50% inhibition at a 3.5 to approximately 4.5-fold lower concentration than the lauroylated peptide in each assay, indicating that the strength of the interaction between T alpha and T beta gamma is altered by heterogeneous fatty acids linked to T alpha. This suggests that a looser subunit interaction in transducin which is due to an abundance of N-linked fatty acids other than myristate would favour the rapid turnover and catalysis essential for the visual excitation in photoreceptor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate Ribose / metabolism
  • Amino Acid Sequence
  • Animals
  • Cattle
  • Fatty Acids / metabolism
  • GTP Phosphohydrolases / antagonists & inhibitors
  • GTP-Binding Proteins / metabolism*
  • Glycine / metabolism
  • In Vitro Techniques
  • Lipid Metabolism*
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Protein Processing, Post-Translational
  • Structure-Activity Relationship
  • Transducin / metabolism*

Substances

  • Fatty Acids
  • Peptide Fragments
  • Adenosine Diphosphate Ribose
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • Transducin
  • Glycine