Fluorescence study of the thyroxine-dependent conformational changes in human serum transthyretin

AbstractFluorescence studies of transthyretin (TTR) were conducted to detect structural changes associated with the environment of its two tryptophans, induced by binding of thyroxine (T4). Non-radiative tryptophans relaxation rate has an activation energy of 6.4 kcal/mol for TTR, which is decreased to 4.4 kcal/mol for TTR-T4 complex. The maximum fluorescence wavelength was red-shifted as the excitation wavelength was increased. T4 changed the magnitude of this shift. T4 binding per se changed the emission maximum reflecting different environments of the tryptophans. Double-quenching experiments also showed that T4 produces changes in the tryptophans environments. These findings were interpreted as the result of structural alterations in the protein matrix induced by T4 which contribute in part to explain the negative cooperativity associated with the occupancy of the second binding site