Identification of a Glycosaminoglycan Binding Surface on Human Interleukin-8
- 24 July 1998
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 37 (32), 11193-11201
- https://doi.org/10.1021/bi972867o
Abstract
The activation of leukocytes by chemokines is believed to be mediated via binding of chemokines to glycosaminoglycan chains of the extracellular matrix. The binding site on the chemokine interleukin-8 (IL-8) for the glycosaminoglycan heparin has been characterized using a systematic series of site-directed mutants of IL-8 in which the basic residues of the protein have been replaced by alanine. Mutation of K64 and R68 caused the largest decrease in affinity for a heparin Sepharose matrix, with smaller effects seen with mutations of K20, R60, and K67. Heparin-derived disaccharides that could disrupt the IL-8-heparin Sepharose interaction were identified by a competitive binding assay. Heteronuclear NMR spectroscopic titration of 15N-labeled IL-8 with a trisulfated disaccharide revealed a cluster of residues on IL-8 which were perturbed by disaccharide binding. These data identify a heparin-binding surface on IL-8 that includes the C-terminal α-helix and the proximal loop around residues 18−23. The heparin-binding site is spatially distinct from the residues involved in receptor binding.Keywords
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