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

TLDR: It is suggested 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.

Abstract: MYRISTATE is a fatty acid (fourteen-carbon chain with no double bonds, C14:0) linked to the amino-terminal glycine of several proteins1–7, including α-subunits of heterotrimeric (α/βγ) G proteins8,9. We report here a novel modification at the N terminus of the α-subunit of the photoreceptor G protein transducin, Tα, with heterogeneous fatty acids composed of laurate (C12:0), unsaturated C14:2 and C14:1 fatty acids, and a small amount (∼5%) of myristate. Both the GTPase activity of Tα/Tβγ and the T/βγ-dependent ADP-ribosylation of Tα catalysed by pertussis toxin were inhibited by the lauroylated and myristoylated N-terminal peptide of Tα. The myristoylated peptide gave 50% inhibition at a 3.5 to ∼4.5-fold lower concentration than the lauroylated peptide in each assay, indicating that the strength of the interaction between Tα and Tβγ is altered by heterogeneous fatty acids linked to Tα. 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.