Functional domains of the fatty acid transport proteins: Studies using protein chimeras

Abstract

SUMMARYFatty acid transport proteins (FATP) function in fatty acid trafficking pathways, several of which have been shown to participate in the transport of exogenous fatty acids into the cell. Members of this protein family also function as acyl CoA synthetases with specificity towards very long chain fatty acids or bile acids. These proteins have two identifying sequence motifs: The ATP/AMP motif, an approximately 100 amino acid segment required for ATP binding and common to members of the adenylate-forming super family of proteins, and the FATP/VLACS motif that consists of approximately 50 amino acid residues and is restricted to members of the FATP family. This latter motif has been implicated in fatty acid transport in the yeast FATP orthologue Fat1p. In the present studies using a yeast strain containing deletions in FAT1 (encoding Fat1p) and FAA1 (encoding the major acyl CoA synthetase (Acsl) Faa1p) as an experimental platform, the phenotypic and functional properties of specific murine FATP1-FATP4 and FATP6-FATP4 protein chimeras were evaluated in order to define elements within these proteins that further distinguish the fatty acid transport and activation functions. As expected from previous work FATP1 and FATP4 were functional in the fatty acid transport pathway, while and FATP6 was not. All three isoforms were able to activate the very long chain fatty acids arachidonate (C 20:4 ) and lignocerate (C 24:0 ), but with distinguishing activities between saturated and highly unsaturated ligands. A 73 amino acid segment common to FATP1 and FATP4 and between the ATP/AMP and FATP/VLACS motifs was identified by studying the chimeras, which is hypothesized to contribute to the transport function.

Membrane Fatty Acid Transporters as Regulators of Lipid Metabolism: Implications for Metabolic Disease

“…Arrowheads and numbers indicate the approximate positions of amino acid residues. [Data compiled from Lewis et al (266) and DiRusso et al (103).] Giant vesicles are formed from parenchymal cells by incubation with an appropriate collagenase for that tissue in a high K ϩ -containing buffer and are harvested by centrifugation (295,332).…”

A novel role for fatty acid transport protein 1 in the regulation of tricarboxylic acid cycle and mitochondrial function in 3T3-L1 adipocytes

“…To assess this, the rate of [2][3][4][5][6][7][8][9][10][11][12][13][14] C]pyruvate oxidation was evaluated as a measure of tricarboxylic acid cycle activity ( 31 ). As shown in Fig.…”

“…Members of the FATP family are integral membrane proteins and exhibit CoA-and ATP-dependent long-chain and very long-chain fatty acyl-CoA synthetase activity (8)(9)(10)(11)(12). FATPs facilitate LCFA infl ux at least in part by coupling the diffusion of LCFA through the plasma membrane with CoAesterifi cation on the inner leafl et of the membrane in a process termed vectoral acylation (13)(14)(15).…”

Actinobacterial Acyl Coenzyme A Synthetases Involved in Steroid Side-Chain Catabolism

“…FATPs are conserved proteins found in humans, mammals, primates, vertebrates, insects, nematodes, fungi, yeasts, and mycobacteria (49,50). These proteins facilitate the transport of LCFAs across biological membranes (50), and some members of this family also possess acylCoA synthetase activities with specificity toward LCFAs and bile acids (51,52). An intriguing possibility is that FadD17 Mtb could be a membrane-associated protein involved in transport and/or CoA thioesterification of fatty acids and/or steroids.…”