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Backbone dynamics of SDF‐1α determined by NMR: Interpretation in the presence of monomer–dimer equilibrium
Author(s) -
Baryshnikova Olga K.,
Sykes Brian D.
Publication year - 2006
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.062255806
Subject(s) - dimer , monomer , chemistry , equilibrium constant , relaxation (psychology) , nuclear magnetic resonance spectroscopy , chemical shift , crystallography , stereochemistry , polymer , organic chemistry , biology , neuroscience
SDF‐1α is a member of the chemokine family implicated in various reactions in the immune system. The interaction of SDF‐1α with its receptor, CXCR4, is responsible for metastasis of a variety of cancers. SDF‐1α is also known to play a role in HIV‐1 pathogenesis. The structures of SDF‐1α 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‐1α determined through measurement of main chain 15 N NMR relaxation data. The data were obtained at several concentrations of SDF‐1α 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‐1α. The experimental relaxation data and the extrapolated data for monomeric SDF‐1α were analyzed using the model free approach. The model free analysis indicated that SDF‐1α 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‐1α.