title: Ligand specificity and conformational stability of human fatty acid-binding proteins.
abstract: Fatty acid binding proteins (FABPs) are small cytosolic proteins with virtually identical backbone structures that facilitate the solubility and intracellular transport of fatty acids. At least eight different types of FABP occur, each with a specific tissue distribution and possibly with a distinct function. To define the functional characteristics of all eight human FABPs, viz. heart (H), brain (B), myelin (M), adipocyte (A), epidermal (E), intestinal (I), liver (L) and ileal lipid-binding protein (I-LBP), we studied their ligand specificity, their conformational stability and their immunological crossreactivity. Additionally, binding of bile acids to I-LBP was studied. The FABP types showed differences in fatty acid binding affinity. Generally, the affinity for palmitic acid was lower than for oleic and arachidonic acid. All FABP types, except E-FABP, I-FABP and I-LBP interacted with 1-anilinonaphtalene-8-sulphonic acid (ANS). Only L-FABP, I-FABP and M-FABP showed binding of 11-((5-dimethylaminonaphtalene-1-sulfonyl)amino)undecanoic acid (DAUDA). I-LBP showed increasing binding of bile acids in the order taurine-conjugated>glycine-conjugated>unconjugated bile acids. A hydroxylgroup of bile acids at position 7 decreased and at position 12 increased the binding affinity to I-LBP. The fatty acid-binding affinity and the conformation of FABP types were differentially affected in the presence of urea. Our results demonstrate significant differences in ligand binding, conformational stability and surface properties between different FABP types which may point to a specific function in certain cells and tissues. The preference of I-LBP (but not L-FABP) for conjugated bile acids is in accordance with a specific role in bile acid reabsorption in the ileum.
authors.affiliation: Department of Biochemistry, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. a.zimmerman@bioch.kun.nl
authors.forename: A W
authors.initials: AW
authors.lastname: Zimmerman
authors.forename: H T
authors.initials: HT
authors.lastname: van Moerkerk
authors.forename: J H
authors.initials: JH
authors.lastname: Veerkamp
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D009363:Neoplasm Proteins; D009928:Organ Specificity; D011487:Protein Conformation; D011489:Protein Denaturation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D025521:Tumor Suppressor Proteins
chemical_list: D001647:Bile Acids and Salts; D002352:Carrier Proteins; C493319:FABP1 protein, human; C493412:FABP5 protein, human; C107608:FABP7 protein, human; C493320:Fabp1 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D008024:Ligands; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins