title: The structural role of receptor tyrosine sulfation in chemokine recognition.
abstract: Tyrosine sulfation is a post-translational modification of secreted and transmembrane proteins, including many GPCRs such as chemokine receptors. Most chemokine receptors contain several potentially sulfated tyrosine residues in their extracellular N-terminal regions, the initial binding site for chemokine ligands. Sulfation of these receptors increases chemokine binding affinity and potency. Although receptor sulfation is heterogeneous, insights into the molecular basis of sulfotyrosine (sTyr) recognition have been obtained using purified, homogeneous sulfopeptides corresponding to the N-termini of chemokine receptors. Receptor sTyr residues bind to a shallow cleft defined by the N-loop and β3-strand elements of cognate chemokines. Tyrosine sulfation enhances the affinity of receptor peptides for cognate chemokines in a manner dependent on the position of sulfation. Moreover, tyrosine sulfation can alter the selectivity of receptor peptides among several cognate chemokines for the same receptor. Finally, binding to receptor sulfopeptides can modulate the oligomerization state of chemokines, thereby influencing the ability of a chemokine to activate its receptor. These results increase the motivation to investigate the structural basis by which tyrosine sulfation modulates chemokine receptor activity and the biological consequences of this functional modulation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic., Australia.
authors.forename: Justin P
authors.initials: JP
authors.lastname: Ludeman
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Stone
mesh_terms: D000818:Animals; D018925:Chemokines / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D019707:Receptors, Chemokine / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D018925:Chemokines; D010455:Peptides; D019707:Receptors, Chemokine; D013431:Sulfates; D014443:Tyrosine
keywords: chemokine; chemokine receptor; structure; tyrosine sulfation