Lipid modification at the N terminus of photoreceptor G-protein alpha-subunit.
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.
Kokame
K
K
Department of Biophysics, Faculty of Science, Kyoto University, Japan.
Fukada
Y
Y
Yoshizawa
T
T
Takao
T
T
Shimonishi
Y
Y
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D005227:Fatty Acids / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D013329:Structure-Activity Relationship; D015293:Transducin / Q000378:metabolism*
D005227:Fatty Acids; D010446:Peptide Fragments; D000246:Adenosine Diphosphate Ribose; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D015293:Transducin; D005998:Glycine