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

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. L'acylation concerne de très nombreuses protéines (enzymes, hormones, récepteurs, oncogènes, suppresseurs de tumeur, protéines impliquées dans la transduction des signaux, protéines de structure eucaryotes et même virales) et exerce donc une grande variété de fonctions dans les régulations cellulaires. La liaison covalente de l'acide gras à la protéine est cruciale pour l'acquisition de la fonction de la protéine, en changeant son hydrophobicité, en régulant l'ancrage de la protéine à la membrane, en modifiant son adressage subcellulaire ou encore en induisant des interactions entre sous-unités protéiques. La découverte progressive de nombreuses protéines acylées, dont la fonction est régulée par l'acylation, donne donc un nouvel intérêt fonctionnel à ces acides gras saturés. L'objectif de cette revue est de synthétiser les découvertes récentes sur les différentes classes d'acylation des protéines et sur les fonctions cellulaires émergentes que cette acylation procure à certains acides gras saturés. Le lien nutritionnel entre ces mécanismes moléculaires et les apports alimentaires en acides gras saturés est finalement discuté.

Modification of plant proteins for improved functionality: A review

“…Fatty acid acylation that involves the attachment of acyl‐CoA derived from short,‐ medium‐, and long‐chain fatty acid covalently to the protein residues, also takes their process name from the fatty acid used. For instance, “palmitoylation” refers to the attachment of palmitic acid (C16:0) to the cysteine residue of proteins (Rioux, 2016).…”

The actions of ghrelin in the paraventricular nucleus: energy balance and neuroendocrine implications

“…The preproghrelin gene produces proghrelin, a prohormone that includes ghrelin and obestatin, the former is then O‐n ‐octanoylated by ghrelin O ‐acyl‐transferase (GOAT). Proghrelin is finally cleaved in order to generate different peptides, which are secreted into the circulation . The octanoylation of ghrelin is necessary for its effects on GHSR since des‐acyl‐ghrelin does not interact with this receptor .…”

Cellular and Molecular Responses of Dunaliella tertiolecta by Expression of a Plant Medium Chain Length Fatty Acid Specific Acyl-ACP Thioesterase

“…There is little information regarding MCFA acylation of proteins in microalgae. However, studies of mammalian, plant, viral, and lower eukaryotic systems have proven the physiological significance of the FA acylation process to mediate protein subcellular localization, protein-protein interaction, or protein-membrane interaction that would control cell volumes ( Stephenson et al, 1989 ; Rioux, 2016 ). The possible linkage characteristics of elevated MCFA levels and protein acylation could be considered for future investigation but meanwhile, it would not be further covered within the scope of this study.…”