Thermodynamics of TRAF-Receptor Interactions

TRAP recruitment requires Hgand-induced changes in receptors that allow simultaneous interactions of each TRAP trimer with three receptor intracellular domains. This observation implicates that monomeric TRAF-receptor interactions are of low affinity so that the interactions do not occur in the absence of receptor activation. A number of quantitative biophysical characterizations with isothermal titration calorimetry (ITC) and surface plasma resonance (SPR) have provided solid support to this view (Table III). 

TRAF solution exhibited excellent agreement with ideal binding, indicating the presence of a single type of binding site and the lack of coopera-tivity in the interaction. 

ITC measurements on TRAF2-receptor interactions have revealed invariably favorable enthalpies and unfavorable entropies, indicating that all these interactions are energetically driven by exothermic enthalpy. The enthalpy of the interaction showed a relative large negative linear dependence with temperature, as measured for the TRAF2-CD30 interaction at 10, 20 and 30°C (Table III). 

The large dependence of enthalpy with temperature is indicative of a specihc interaction, even though that the affinities of these monomeric interactions between TRAF2 and receptors are rather low. As suggested from thermodynamic studies of protein-DNA interactions, a non-specific weak complex held together by electrostatic forces often exhibits little temperature dependence of enthalpy (Ladbury, 1995). 

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