Thermodynamics of triiodothyronine nuclear receptor interaction. Role of hydrophobicity in triiodothyronine binding to its receptor.
We have investigated the thermodynamic properties of triiodothyronine (T3)-solubilized hepatic nuclear receptor interaction. These studies revealed that the equilibrium constant was markedly dependent on temperature and van't Hoff plots revealed a significant deviation from linearity. Both enthalpy and entropy changes decreased with increasing temperature such that at 37 degrees C both were negative. (delta H0 -27.1 kcal/mol; delta S0, -45.1 cal/mol.deg; and the heat capacity delta Cp0 (25 degrees C), -759 cal/mol.deg). Several T3 analogues revealed similar thermodynamic characteristics. Our finding that the T3-receptor interaction is characterized by a negative heat capacity is compatible with the previous proposal of hydrophobic bonding by Jorgensen. The large negative entropy change at 37 degrees C for T3-receptor reaction is in contrast to the more positive entropy values for several T3-plasma protein reactions. One possible explanation of this difference in entropy values between the nuclear receptor and plasma proteins is that T3 induces a conformational change in the receptor, a concept supported by previous data from our laboratory indicating that the occupation of the T3 receptor results in an alteration in the chromatographic migration of the receptor.
D000818:Animals; D001667:Binding, Competitive; D002467:Cell Nucleus / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008433:Mathematics; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013816:Thermodynamics; D013963:Thyroid Hormones / Q000378:metabolism*; D013965:Thyroidectomy; D014284:Triiodothyronine / Q000378:metabolism*
D011956:Receptors, Cell Surface; D013963:Thyroid Hormones; D014284:Triiodothyronine