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Aggregation-independent modulation of proteoglycan binding by neutralization of C-terminal acidic residues in the chemokine macrophage inflammatory protein 1alpha.

TitleAggregation-independent modulation of proteoglycan binding by neutralization of C-terminal acidic residues in the chemokine macrophage inflammatory protein 1alpha.
Publication TypeJournal Article
Year of Publication2001
AuthorsOttersbach K, Graham GJ
JournalBiochem J
Volume354
IssuePt 2
Pagination447-53
Date Published2001 Mar 1
ISSN0264-6021
KeywordsAnimals, Blotting, Western, Cells, Cultured, Chemokine CCL3, Chemokine CCL4, Chromatography, Affinity, Chromatography, Gel, Enzyme-Linked Immunosorbent Assay, Heparin, Macrophage Inflammatory Proteins, Mice, Protein Conformation, Proteoglycans
Abstract

Members of the chemokine family of proteins mediate their biological effects through interaction with a family of seven-transmembrane G-protein-coupled receptors. This interaction is complicated by the biochemical properties of chemokines, such as their ability to form self aggregates and their ability to bind to proteoglycans. With some chemokines there is a clear interrelationship between these interactions; the chemokine platelet factor 4 binds preferentially to proteoglycans in its aggregated form. Little is known about the role of aggregation in the proteoglycan binding of other chemokines. Here we demonstrate that the aggregation status of the chemokine macrophage inflammatory protein 1alpha (MIP-1alpha) has no detectable effect on its affinity for proteoglycans. Furthermore, we demonstrate that the alteration of acidic amino acid residues in MIP-1alpha influences the affinity of its interactions with heparin as these residues are progressively neutralized, leading to an enhanced binding affinity for heparin. Thus, with MIP-1alpha, aggregation is not a determinant of proteoglycan binding; however, overall charge does seem to have a major role in the interaction. These results therefore add to our understanding of the nature of the interaction between MIP-1alpha and proteoglycans and suggests that the basic amino acids might not be the sole regulators of proteoglycan binding.

Alternate JournalBiochem. J.
PubMed ID11171125
PubMed Central IDPMC1221674
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