Ligand specificity and conformational dependence of the hepatic nuclear factor-4alpha (HNF-4alpha ). Academic Article uri icon

abstract

  • Hepatic nuclear factor-4alpha (HNF-4alpha) controls the expression of genes encoding proteins involved in lipid and carbohydrate metabolism. Fatty acyl-CoA thioesters have recently been proposed to be naturally occurring ligands of HNF-4alpha and to regulate its transcriptional activity as function of their chain length and degree of unsaturation (Hertz, R., Magenheim, J., Berman, I., and Bar-Tana, J. (1998) Nature 392, 512-516). However, the apparent low affinities (microm K(d) values) obtained with a radiolabeled fatty acyl-CoA ligand binding assay raised questions regarding the physiological significance of this finding. Furthermore, it is not known whether interaction with fatty acyl-CoA alters the structure of HNF-4alpha. These issues were examined using rat recombinant HNF-4alpha ligand-binding domain (HNF-4alphaLBD) in conjunction with photon counting fluorescence and circular dichroism. First, fluorescence resonance energy transfer between HNF-4alphaLBD tryptophan (Trp) and cis-parinaroyl-CoA yielded an intermolecular distance of

published proceedings

  • J Biol Chem

author list (cited authors)

  • Petrescu, A. D., Hertz, R., Bar-Tana, J., Schroeder, F., & Kier, A. B.

citation count

  • 65

complete list of authors

  • Petrescu, Anca D||Hertz, Rachel||Bar-Tana, Jacob||Schroeder, Friedhelm||Kier, Ann B

publication date

  • July 2002