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Identification and characterization of a glycosaminoglycan recognition element of the C chemokine lymphotactin. J Biol Chem 2004 Mar 26;279(13):12598-604 PMID: 14707146

Abstract

Chemokine-mediated recruitment of leukocytes in vivo depends on interactions with cell surface glycosaminoglycans. Lymphotactin, the unique member of the "C" chemokine subclass, is a highly basic protein that binds heparin, a glycosaminoglycan, with high affinity (approximately 10 nm). We detected lymphotactin-heparin binding by NMR and mapped this interaction to a narrow surface that wraps around the protein. Substitutions in and around this binding site and surface plasmon resonance analysis of heparin binding affinity identified two arginine residues of lymphotactin as critical for glycosaminoglycan binding. Both arginine mutant proteins and the combined double mutant had dramatically diminished in vivo activity in a leukocyte recruitment assay, suggesting that the lymphotactin-glycosaminoglycan interactions detected in vitro are important for the function of this chemokine. Our results demonstrate that like other chemokines, lymphotactin utilizes highly specific glycosaminoglycan-binding sites that represent potential targets for drug development.

Author List

Peterson FC, Elgin ES, Nelson TJ, Zhang F, Hoeger TJ, Linhardt RJ, Volkman BF

Authors

Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin
Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Arginine
Binding Sites
Chemokines
Chemokines, C
Cloning, Molecular
Codon
Escherichia coli
Glycosaminoglycans
Heparin
Humans
Kinetics
Leukocytes
Lymphokines
Magnetic Resonance Spectroscopy
Models, Molecular
Mutagenesis, Site-Directed
Mutation
Protein Binding
Protein Conformation
Protein Folding
Recombinant Proteins
Sialoglycoproteins
Surface Plasmon Resonance
Time Factors



View this publication's entry at the Pubmed website PMID: 14707146
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