Y. Honma et al., EVIDENCE FOR CONFORMATIONAL CHANGE OF FATTY-ACID-BINDING PROTEIN ACCOMPANYING BINDING OF HYDROPHOBIC LIGANDS, Journal of Biochemistry, 116(5), 1994, pp. 1025-1029
Conformational change of rat liver fatty acid-binding protein was inve
stigated by making use of change of protease-susceptibility in the pre
sence or absence of bound oleic acid and clofibrate. Delipidated fatty
acid-binding protein was rapidly digested by Achromobacter lysyl endo
peptidase, bovine alpha-chymotrypsin, and Staphylococcal V8 protease,
while protein recombined with oleic acid was strongly refractory to pr
oteolysis. This observation indicates that a striking change in the co
nformational state of the protein occurred upon lipid binding, and see
ms to support the recent hypothesis that the large segment homologous
to fatty acid-binding proteins found in a fatty acid-regulated ion cha
nnel constitutes a regulatory domain of the channel [Petrou, S., Ordwa
y, R.W., Singer, J.J., and Walsh, J.V., Jr. (1993) Trends Biochem. Sci
. 18, 41-42]. Clofibrate, which is a potent peroxisome proliferator an
d structurally unrelated to oleic acid, also conferred similar proteas
e resistance upon the protein. A possible physiological aspect of the
present observation is that the cellular level of free fatty acids, wh
ich have metabolic importance and cytotoxicity as well, regulates the
turnover rate of fatty acid-binding proteins by modulating the proteas
e susceptibility of the protein.