Diversity of fatty acid-binding protein structure and function: studies with fluorescent ligands.
The mammalian fatty acid-binding proteins (FABP) are localized in many distinct cell types. They bind long chain fatty acids in vitro, however, their functions and mechanisms of action in vivo remain unknown. The present studies have sought to understand the relationships among these proteins, and to address the possible role of FABP in cellular fatty acid traffic. A series of anthroyloxy-labeled fluorescent fatty acids have been used to examine the physicochemical properties of the fatty acid-binding sites of different members of the FABP family. The fatty acid probes have also been used to study the rate and mechanism of fatty acid transfer from different FABP types to phospholipid membranes. The results of these studies show a number of interesting and potentially important differences between FABP family members. An examination of adipocyte and heart FABP (A- and H-FABP) shows that their fatty acid-binding sites are less hydrophobic than the liver FABP (L-FABP) site, and that the bound ligand experiences less motional constraint within the A- and H-FABP binding sites than within the L-FABP binding site. In keeping with these differences in structural properties, it was found that anthroyloxy-fatty acid transfer from A- and H-FABP to membranes is markedly faster than from L-FABP. Moreover, the mechanism of fatty acid transfer was found to be similar for the highly homologous A- and H-FABP, whereby transfer to phospholipid membranes appears to occur via transient collisional interactions between the FABP and membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
Storch
J
J
Department of Nutritional Sciences, Rutgers University, New Brunswick, New Jersey 08903.
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000737:chemistry*; D005456:Fluorescent Dyes; D006801:Humans; D008024:Ligands; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; C493319:FABP1 protein, human; C107608:FABP7 protein, human; C493320:Fabp1 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D005456:Fluorescent Dyes; D008024:Ligands; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins