DETERMINATION OF THE MONOMER-DIMER EQUILIBRIUM OF INTERLEUKIN-8 REVEALS IT IS A MONOMER AT PHYSIOLOGICAL CONCENTRATIONS

Interleukin-8 has been shown by X-ray crystallography and NMR to be a homodimer, suggesting that this is the form which binds to its recepto r. Here we measure, for the first time, the monomer-dimer equilibrium of interleukin-8 using analytical ultracentrifugation and titration mi crocalorimetry and find that it dissociates readily to monomers with a n equilibrium dissociation constant of 18 +/- 6 mu M at 37 degrees C. The present findings suggest that the monomer is the form which binds to the receptor. Comparison of experimental and structure-based calcul ated thermodynamics of interleukin-8 dimerization argues for limited s ubunit conformational changes upon dissociation to monomer.