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Backbone dynamics of SDF-1 determined by NMR: Interpretation in the presence of monomer–dimer equilibrium

Department of Biochemistry and Protein Engineering Network of Centres of Excellence, University of Alberta, Edmonton, Alberta T6G 2S2, Canada

(RECEIVED March 30, 2006; FINAL REVISION August 2, 2006; ACCEPTED August 2, 2006)

SDF-1 is a member of the chemokine family implicated in various reactions in the immune system. The interaction of SDF-1 with its receptor, CXCR4, is responsible for metastasis of a variety of cancers. SDF-1 is also known to play a role in HIV-1 pathogenesis. The structures of SDF-1 determined by NMR spectroscopy have been shown to be monomeric while X-ray structures are dimeric. Biochemical data and in vivo studies suggest that dimerization is likely to be important for the function of chemokines. We report here the dynamics of SDF-1 determined through measurement of main chain ¹⁵N NMR relaxation data. The data were obtained at several concentrations of SDF-1 and used to determine a dimerization constant of 5 mM for a monomer–dimer equilibrium. The dimerization constant was subsequently used to extrapolate values for the relaxation data corresponding to monomeric SDF-1. The experimental relaxation data and the extrapolated data for monomeric SDF-1 were analyzed using the model free approach. The model free analysis indicated that SDF-1 is rigid on the nano- to picosecond timescale with flexible termini. Several residues involved in the dimer interface display slow micro- to millisecond timescale motions attributable to chemical exchange such as monomer–dimer equilibrium. NMR relaxation measurements are shown to be applicable for studying oligomerization processes such as the dimerization of SDF-1.

Keywords: backbone dynamics; NMR; chemokine; SDF-1; monomer–dimer equilibrium

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