Fatty acid acylation of proteins: specific roles for palmitic, myristic and caprylic acids

Vincent Rioux

doi:10.1051/ocl/2015070

Abstract

Fatty acid acylation of proteins corresponds to the co- or post-translational covalent linkage of an acyl-CoA, derived from a fatty acid, to an amino-acid residue of the substrate protein. The cellular fatty acids which are involved in protein acylation are mainly saturated fatty acids. Palmitoylation (S-acylation) corresponds to the reversible attachment of palmitic acid (C16:0) via a thioester bond to the side chain of a cysteine residue. N-terminal myristoylation refers to the covalent attachment of myristic acid (C14:0) by an amide bond to the N-terminal glycine of many eukaryotic and viral proteins. Octanoylation (O-acylation) typically concerns the formation of an ester bond between octanoic acid (caprylic acid, C8:0) and the side chain of a serine residue of the stomach peptide ghrelin. An increasing number of proteins (enzymes, hormones, receptors, oncogenes, tumor suppressors, proteins involved in signal transduction, eukaryotic and viral structural proteins) have been shown to undergo fatty acid acylation. The addition of the acyl moiety is required for the protein function and usually mediates protein subcellular localization, protein-protein interaction or protein-membrane interaction. Therefore, through the covalent modification of proteins, these saturated fatty acids exhibit emerging specific and important roles in modulating protein functions. This review provides an overview of the recent findings on the various classes of protein acylation leading to the biological ability of saturated fatty acids to regulate many pathways. Finally, the nutritional links between these elucidated biochemical mechanisms and the physiological roles of dietary saturated fatty acids are discussed.

Highlights

Fatty acid acylation of proteins (Towler et al, 1988) corresponds to the co- or post-translational covalent linkage of a fatty acid, activated in the form of acyl-CoA, to an aminoacid residue of the substrate protein (Fig. 1)
The description of this regulatory mechanism highlighted a new potential relationship between myristic acid, the saturated fatty acid capable of binding and activating the enzyme involved in the final de novo ceramide biosynthesis step, and lipoapoptosis induced through the ceramide pathway
The stomach enzyme involved in ghrelin octanoylation is called ghrelin O-acyltransferase (GOAT) and belongs to the family of membrane bound O-acyltransferases (MBOAT), a group of proteins involved in acetyltransferase and acyltransferase activity (Gutierrez et al, 2008)

Summary

Introduction

Fatty acid acylation of proteins (Towler et al, 1988) corresponds to the co- or post-translational covalent linkage of a fatty acid, activated in the form of acyl-CoA, to an aminoacid residue of the substrate protein (Fig. 1). The cellular fatty acids covalently bound to proteins are mainly saturated fatty acids (SFAs). Palmitoylation (S-acylation) corresponds to the reversible attachment of palmitic acid (C16:0) to the side chain of a cysteine residue via a thioester bond (Blaskovic et al, 2014). N-terminal myristoylation refers to the covalent attachment of myristic acid (C14:0) by an amide bond to the N-terminal glycine of many eukaryotic and viral proteins (Johnson, Bhatnagar, et al, 1994). Through the covalent modification of proteins, these particular saturated fatty acids exhibit emerging specific and important roles in modulating protein functions (Ezanno et al, 2013)

Palmitic acid and protein palmitoylation

Myristic acid and protein N-terminal myristoylation

Caprylic acid and ghrelin octanoylation

Impact of dietary SFAs on cellular protein acylation

Findings

Conclusion