title: Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12).
abstract: Tyrosine sulfation of the chemokine receptor CXCR4 enhances its interaction with the chemokine SDF-1alpha. Given similar post-translational modification of other receptors, including CCR5, CX3CR1 and CCR2b, tyrosine sulfation may be of universal importance in chemokine signaling. N-terminal domains from seven transmembrane chemokine receptors have been employed for structural studies of chemokine-receptor interactions, but never in the context of proper post-translational modifications known to affect function. A CXCR4 peptide modified at position 21 by expressed tyrosylprotein sulfotransferase-1 and unmodified peptide are both disordered in solution, but bind SDF-1alpha with low micromolar affinities. NMR and fluorescence polarization measurements showed that the CXCR4 peptide stabilizes dimeric SDF-1alpha, and that sulfotyrosine 21 binds a specific site on the chemokine that includes arginine 47. We conclude that the SDF-1alpha dimer preferentially interacts with receptor peptide, and residues beyond the extreme N-terminal region of CXCR4, including sulfotyrosine 21, make specific contacts with the chemokine ligand.
authors.affiliation: Department of Biochemistry, Medical College of Wisconsin, Milwaukee, 53226, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Veldkamp
authors.forename: Christoph
authors.initials: C
authors.lastname: Seibert
authors.forename: Francis C
authors.initials: FC
authors.lastname: Peterson
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Sakmar
authors.forename: Brian F
authors.initials: BF
authors.lastname: Volkman
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism*; D019281:Dimerization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D019718:Receptors, CXCR4 / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4; C005662:tyrosine O-sulfate; D014443:Tyrosine