STOICHIOMETRY AND THERMODYNAMICS OF THE INTERACTION BETWEEN THE FC FRAGMENT OF HUMAN IGG(1) AND ITS LOW-AFFINITY RECEPTOR FC-GAMMA-RIII

IgG-Fc receptors, cell surface glycoproteins binding the Fc region of antibodies, play a crucial role in the immune system. To better understand the nature of the recognition process, we have examined the interaction between huIgG(1)-Fc and a soluble fragment of huFc gamma RIII (sCD16). Analytical ultracentrifugation experiments clearly demonstrate that IgG(1)-Fc and sCD 16 interact weakly to form a 1:1 complex with an association constant of 1.7 x 10(5) M(-1) in PBS at 22.0 degrees C. The thermodynamic parameters, obtained from the temperature dependence of the equilibrium binding constants, exhibit an enthalpy-entropy compensation with a favorable enthalpy at physiological temperatures. The Value of -360 cal mol(-1) K-1 for Delta C-p degrees possibly identifies the process as one in which local folding/rearrangement is coupled to complex formation. The 1:1 stoichiometry and thermodynamic parameters provide a basis for understanding the nature of the Fc gamma R-IgG interactions.