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

14 Citations (Scopus)

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

Fingerprint

Chemokine CCL5
Chondroitin Sulfates
Glycosaminoglycans
Ligands
Galactosamine
Chemokine Receptors
Oligosaccharides
Magnetic Resonance Spectroscopy
Inflammation

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

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

Interactions of the Chemokine CCL5/RANTES with Medium-Sized Chondroitin Sulfate Ligands. / Deshauer, Courtney; Morgan, Ashli M.; Ryan, Eathen O.; Handel, Tracy M.; Prestegard, James H.; Wang, Xu.

In: Structure, Vol. 23, No. 6, 3158, 03.06.2015, p. 1066-1077.

Research output: Contribution to journalArticle

Deshauer, C, Morgan, AM, Ryan, EO, Handel, TM, Prestegard, JH & Wang, X 2015, 'Interactions of the Chemokine CCL5/RANTES with Medium-Sized Chondroitin Sulfate Ligands', Structure, vol. 23, no. 6, 3158, pp. 1066-1077. https://doi.org/10.1016/j.str.2015.03.024
Deshauer, Courtney ; Morgan, Ashli M. ; Ryan, Eathen O. ; Handel, Tracy M. ; Prestegard, James H. ; Wang, Xu. / Interactions of the Chemokine CCL5/RANTES with Medium-Sized Chondroitin Sulfate Ligands. In: Structure. 2015 ; Vol. 23, No. 6. pp. 1066-1077.
@article{75d7bff01e85458aa63d709786124d70,
title = "Interactions of the Chemokine CCL5/RANTES with Medium-Sized Chondroitin Sulfate Ligands",
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.",
author = "Courtney Deshauer and Morgan, {Ashli M.} and Ryan, {Eathen O.} and Handel, {Tracy M.} and Prestegard, {James H.} and Xu Wang",
year = "2015",
month = "6",
day = "3",
doi = "10.1016/j.str.2015.03.024",
language = "English (US)",
volume = "23",
pages = "1066--1077",
journal = "Structure with Folding & design",
issn = "0969-2126",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - Interactions of the Chemokine CCL5/RANTES with Medium-Sized Chondroitin Sulfate Ligands

AU - Deshauer, Courtney

AU - Morgan, Ashli M.

AU - Ryan, Eathen O.

AU - Handel, Tracy M.

AU - Prestegard, James H.

AU - Wang, Xu

PY - 2015/6/3

Y1 - 2015/6/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84930384439&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930384439&partnerID=8YFLogxK

U2 - 10.1016/j.str.2015.03.024

DO - 10.1016/j.str.2015.03.024

M3 - Article

C2 - 25982530

AN - SCOPUS:84930384439

VL - 23

SP - 1066

EP - 1077

JO - Structure with Folding & design

JF - Structure with Folding & design

SN - 0969-2126

IS - 6

M1 - 3158

ER -