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Structure and function of the glycosaminoglycan binding site of chemokine macrophage-inflammatory protein-1 beta.

Publication ,  Journal Article
Koopmann, W; Ediriwickrema, C; Krangel, MS
Published in: J Immunol
August 15, 1999

The ability of chemokines to bind to glycosaminoglycans (GAGs) on cell surfaces and in the extracellular matrix is thought to play a crucial role in chemokine function. We investigated the structural basis for chemokine binding to GAGs by using in vitro mutagenesis to identify amino acids of chemokine macrophage-inflammatory protein-1 beta (MIP-1 beta) that contribute to its interaction with the model GAG heparin. Among six basic residues that are organized into a single basic domain in the folded MIP-1 beta monomer, three (R18, K45, and R46) were found to contribute significantly to heparin binding. Of these, R46 was found to play a dominant role, and proved essential for the interaction of MIP-1 beta with both heparin and heparan sulfate in physiological salt. The results of this mutational analysis have implications for the structure of the MIP-1 beta-heparin complex, and a comparison of these results with those obtained by mutational analysis of the MIP-1 alpha-heparin interaction suggests a possible structural difference between the MIP-1 beta-heparin and MIP-1 alpha-heparin complexes. To determine whether GAG binding plays an important role in receptor binding and cellular activation by MIP-1 beta, the activities of wild-type MIP-1 beta and R46-substituted MIP-1 beta were compared in assays of T lymphocyte chemotaxis. The two proteins proved equipotent in this assay, arguing that interaction of MIP-1 beta with GAGs is not intrinsically required for functional interaction of MIP-1 beta with its receptor.

Duke Scholars

Published In

J Immunol

ISSN

0022-1767

Publication Date

August 15, 1999

Volume

163

Issue

4

Start / End Page

2120 / 2127

Location

United States

Related Subject Headings

  • Structure-Activity Relationship
  • Mutagenesis, Site-Directed
  • Models, Molecular
  • Mast Cells
  • Macrophage Inflammatory Proteins
  • Immunology
  • Humans
  • Heparin
  • Glycosaminoglycans
  • Chromatography, Agarose
 

Citation

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MLA
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Koopmann, W., Ediriwickrema, C., & Krangel, M. S. (1999). Structure and function of the glycosaminoglycan binding site of chemokine macrophage-inflammatory protein-1 beta. J Immunol, 163(4), 2120–2127.
Koopmann, W., C. Ediriwickrema, and M. S. Krangel. “Structure and function of the glycosaminoglycan binding site of chemokine macrophage-inflammatory protein-1 beta.J Immunol 163, no. 4 (August 15, 1999): 2120–27.
Koopmann W, Ediriwickrema C, Krangel MS. Structure and function of the glycosaminoglycan binding site of chemokine macrophage-inflammatory protein-1 beta. J Immunol. 1999 Aug 15;163(4):2120–7.
Koopmann, W., et al. “Structure and function of the glycosaminoglycan binding site of chemokine macrophage-inflammatory protein-1 beta.J Immunol, vol. 163, no. 4, Aug. 1999, pp. 2120–27.
Koopmann W, Ediriwickrema C, Krangel MS. Structure and function of the glycosaminoglycan binding site of chemokine macrophage-inflammatory protein-1 beta. J Immunol. 1999 Aug 15;163(4):2120–2127.

Published In

J Immunol

ISSN

0022-1767

Publication Date

August 15, 1999

Volume

163

Issue

4

Start / End Page

2120 / 2127

Location

United States

Related Subject Headings

  • Structure-Activity Relationship
  • Mutagenesis, Site-Directed
  • Models, Molecular
  • Mast Cells
  • Macrophage Inflammatory Proteins
  • Immunology
  • Humans
  • Heparin
  • Glycosaminoglycans
  • Chromatography, Agarose