Evidence for conformational change of fatty acid-binding protein accompanying binding of hydrophobic ligands.
Conformational change of rat liver fatty acid-binding protein was investigated by making use of change of protease-susceptibility in the presence or absence of bound oleic acid and clofibrate. Delipidated fatty acid-binding protein was rapidly digested by Achromobacter lysyl endopeptidase, bovine alpha-chymotrypsin, and Staphylococcal V8 protease, while protein recombined with oleic acid was strongly refractory to proteolysis. This observation indicates that a striking change in the conformational state of the protein occurred upon lipid binding, and seems to support the recent hypothesis that the large segment homologous to fatty acid-binding proteins found in a fatty acid-regulated ion channel constitutes a regulatory domain of the channel [Petrou, S., Ordway, R.W., Singer, J.J., and Walsh, J.V., Jr. (1993) Trends Biochem. Sci. 18, 41-42]. Clofibrate, which is a potent peroxisome proliferator and structurally unrelated to oleic acid, also conferred similar protease resistance upon the protein. A possible physiological aspect of the present observation is that the cellular level of free fatty acids, which have metabolic importance and cytotoxicity as well, regulates the turnover rate of fatty acid-binding proteins by modulating the protease susceptibility of the protein.
Honma
Y
Y
Department of Biology, Faculty of Science, Niigata University.
Niimi
M
M
Uchiumi
T
T
Takahashi
Y
Y
Odani
S
S
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000302:isolation & purification*; D002918:Chymotrypsin; D002994:Clofibrate / Q000494:pharmacology*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D066298:In Vitro Techniques; D008666:Metalloendopeptidases; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011487:Protein Conformation; D051381:Rats; D012697:Serine Endopeptidases
D002352:Carrier Proteins; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012697:Serine Endopeptidases; D002918:Chymotrypsin; C036813:lysyl endopeptidase; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus; D002994:Clofibrate