Stoichiometry and thermodynamics of the interaction between the Fc fragment of human IgG1 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 huIgG1-Fc and a soluble fragment of huFc gamma RIII (sCD16). Analytical ultracentrifugation experiments clearly demonstrate that IgG1-Fc and sCD16 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 Cp zero 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.
Ghirlando
R
R
Laboratory of Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Keown
M B
MB
Mackay
G A
GA
Lewis
M S
MS
Unkeless
J C
JC
Gould
H J
HJ
D000595:Amino Acid Sequence; D002151:Calorimetry; D002240:Carbohydrate Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry* / Q000378:metabolism*; D007074:Immunoglobulin G / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D007700:Kinetics; D008433:Mathematics; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology; D017452:Receptors, IgG / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D017452:Receptors, IgG