Acyl-CoA binding proteins inhibit the nonenzymic S-acylation of cysteinyl-containing peptide sequences by long-chain acyl-CoAs.
Acyl-CoA binding proteins (ACBPs) from rat and bovine liver were found to inhibit the nonenzymic S-acylation of two representative types of peptides by long-chain acyl-CoAs. As demonstrated previously [Quesnel, S. & Silvius, J. R. (1994) Biochemistry 33 13340-13348; Bharadwaj, M., & Bizzozero, O. A. (1995) J. Neurochem. 65, 1805-1815], peptides with the sequences myristoyl-GCG, myristoyl-GCV, and IRYCWLRR-NH2, all representing physiological S-acylation sites in mammalian proteins, become S-acylated at appreciable rates in the presence of long-chain acyl-CoAs and large unilamellar lipid vesicles. Addition of ACBP at physiological molar ratios with respect to long-chain acyl-CoAs strongly inhibits the spontaneous S-acylation reaction, in a manner that can be quantitatively described by assuming that the ACBP sequesters the acyl-CoA with nanomolar affinity in a complex unable to serve as an S-acyl donor. From these results, we calculate that at physiological (intracellular) concentrations of ACBP, long-chain acyl-CoAs, and membrane lipids the expected half-times for spontaneous S-acylation of such protein sequences by long-chain acyl-CoAs will lie in the range of several tens of hours. The nonenzymic reaction of protein cysteine residues with long-chain acyl-CoAs is thus unlikely to contribute significantly to the physiological modification of signaling and other proteins that show relatively rapid rates of S-acylation in mammalian cells. However, it cannot be excluded that a nonenzymic reaction with long-chain acyl-CoAs could contribute to the physiological S-acylation of certain membrane proteins if the latter exhibit very slow kinetics of S-acylation in vivo.
Leventis
R
R
Department of Biochemistry, McGill University, Montréal, Québec, Canada.
Juel
G
G
Knudsen
J K
JK
Silvius
J R
JR
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000215:Acylation / Q000187:drug effects; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D002352:Carrier Proteins / Q000494:pharmacology*; D003545:Cysteine / Q000737:chemistry* / Q000378:metabolism; D026261:Diazepam Binding Inhibitor; D008081:Liposomes / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D009227:Myristic Acids / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats
D000214:Acyl Coenzyme A; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D008081:Liposomes; D009227:Myristic Acids; D009842:Oligopeptides; D010455:Peptides; C021149:bimanes; D003545:Cysteine