Interactions of the Chemokine CCL5/RANTES with Medium-Sized Chondroitin Sulfate Ligands

Courtney Deshauer, Ashli M. Morgan, Eathen O. Ryan, Tracy M. Handel, James H. Prestegard, Xu Wang

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Summary 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.

Original languageEnglish (US)
Article number3158
Pages (from-to)1066-1077
Number of pages12
JournalStructure
Volume23
Issue number6
DOIs
StatePublished - Jun 3 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

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    Deshauer, C., Morgan, A. M., Ryan, E. O., Handel, T. M., Prestegard, J. H., & Wang, X. (2015). Interactions of the Chemokine CCL5/RANTES with Medium-Sized Chondroitin Sulfate Ligands. Structure, 23(6), 1066-1077. [3158]. https://doi.org/10.1016/j.str.2015.03.024