title: Interactions of the Chemokine CCL5/RANTES with Medium-Sized Chondroitin Sulfate Ligands.
abstract: Interactions of the chemokine CCL5 (RANTES) with glycosaminoglycans (GAGs) are crucial to the CCL5-mediated inflammation process. However, structural information on interactions between CCL5 and longer GAG fragments is lacking. In this study, the interactions between oligosaccharides derived from chondroitin sulfate and a dimeric variant of CCL5 were investigated using solution nuclear magnetic resonance. The data indicate that, in addition to the BBXB motif in the 40s loop, GAGs also contact residues in the N loop in a manner similar to interactions between chemokine and the receptor N terminus, leading to possible stabilization of the dimer. Using 2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl-tagged hexasaccharides, the binding orientation of the hexasaccharides was shown to be highly dependent on the sulfation pattern of the N-acetyl galactosamine groups. Finally, a model of the CCL5 dimer complexed to chondroitin sulfate hexasaccharides was constructed using paramagnetic relaxation enhancement and intra- and intermolecular nuclear Overhauser effect constraints.
authors.affiliation: Department of Chemistry & Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Deshauer
authors.affiliation: Department of Chemistry & Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Ashli M
authors.initials: AM
authors.lastname: Morgan
authors.affiliation: Department of Chemistry & Biochemistry, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Eathen O
authors.initials: EO
authors.lastname: Ryan
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Science, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Handel
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30605, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Prestegard
authors.affiliation: Department of Chemistry & Biochemistry, Arizona State University, Tempe, AZ 85287, USA. Electronic address: xuwang@asu.edu.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
mesh_terms: D018946:Chemokine CCL5 / Q000737:chemistry* / Q000378:metabolism*; D002809:Chondroitin Sulfates / Q000378:metabolism*; D019281:Dimerization; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009844:Oligosaccharides / Q000378:metabolism*; D010880:Piperidines / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry; D011487:Protein Conformation
chemical_list: D018946:Chemokine CCL5; D008024:Ligands; D009844:Oligosaccharides; D010880:Piperidines; D011134:Polysaccharides; C551336:2,2,6,6-tetramethylpiperidide; D002809:Chondroitin Sulfates