The structure of crystalline Escherichia coli-derived rat intestinal fatty acid-binding protein at 2.5-A resolution.
Rat intestinal fatty acid-binding protein (I-FABP) is an abundant cytoplasmic protein which is synthesized in the small intestinal lining cell where it is thought to participate in the absorption and intracellular metabolism of fatty acids. Each mole of this 132-residue polypeptide binds 1 mol of long chain fatty acid in a noncovalent fashion. Because of its small size and single ligand-binding site, I-FABP represents an attractive model for defining the molecular details of long chain fatty acid-protein interactions. The structure of Escherichia coli-derived rat I-FABP has now been solved to 2.5 A resolution using three isomorphous heavy atom derivatives. The protein consists of 10 anti-parallel beta-strands present as two orthogonal beta-sheets. Together a "clam shell-like" structure is formed with an opening located between two beta-strands and an interior that is lined with the side chains of nonpolar amino acids. The bound fatty acid ligand is located in the interior of the protein and has a bent conformation, possibly reflecting the presence of several gauche bonds in the hydrocarbon tail. Our present interpretation of the electron density map suggests that the fatty acid is oriented with its carboxylate group facing the guanidinium group of Arg127, whereas the end of its hydrocarbon tail is in close proximity to Val106. The indole side chain of Trp83 forms the molecular framework around which the principal bend of the hydrocarbon chain occurs.
Sacchettini
J C
JC
Department of Biological Chemistry, Washington University School of Medicine, St. Louis, Missouri 63110.
Gordon
J I
JI
Banaszak
L J
LJ
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D004926:Escherichia coli / Q000378:metabolism*; D005091:Exons; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007421:Intestine, Small / Q000032:analysis*; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011487:Protein Conformation; D051381:Rats; D013816:Thermodynamics; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; C107608:FABP7 protein, human; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins