title: Determination of the monomer-dimer equilibrium of interleukin-8 reveals it is a monomer at physiological concentrations.
abstract: 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 receptor. Here we measure, for the first time, the monomer-dimer equilibrium of interleukin-8 using analytical ultracentrifugation and titration microcalorimetry and find that it dissociates readily to monomers with an equilibrium dissociation constant of 18 +/- 6 microM 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 calculated thermodynamics of interleukin-8 dimerization argues for limited subunit conformational changes upon dissociation to monomer.
authors.affiliation: Department of Macromolecular Sciences, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406.
authors.forename: S D
authors.initials: SD
authors.lastname: Burrows
authors.forename: M L
authors.initials: ML
authors.lastname: Doyle
authors.forename: K P
authors.initials: KP
authors.lastname: Murphy
authors.forename: S G
authors.initials: SG
authors.lastname: Franklin
authors.forename: J R
authors.initials: JR
authors.lastname: White
authors.forename: I
authors.initials: I
authors.lastname: Brooks
authors.forename: D E
authors.initials: DE
authors.lastname: McNulty
authors.forename: M O
authors.initials: MO
authors.lastname: Scott
authors.forename: J R
authors.initials: JR
authors.lastname: Knutson
authors.forename: D
authors.initials: D
authors.lastname: Porter
mesh_terms: D002151:Calorimetry; D004926:Escherichia coli; D005454:Fluorescence Polarization; D006801:Humans; D016209:Interleukin-8 / Q000737:chemistry*; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D013816:Thermodynamics; D014461:Ultracentrifugation
chemical_list: D016209:Interleukin-8; D046911:Macromolecular Substances; D011994:Recombinant Proteins