Loading…
Defining the Interleukin-8-binding Domain of Heparan Sulfate
Interleukin-8, a member of the C X C chemokine family, has been shown to bind to glycosaminoglycans. It has been suggested that heparan sulfate on cell surfaces could provide specific ligand sites on endothelial cells to retain the highly diffusible inflammatory chemokine for presentation to leukocy...
Saved in:
Published in: | Journal of chemical biology 1998-06, Vol.273 (25), p.15487-15493 |
---|---|
Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Interleukin-8, a member of the C X C chemokine family, has been shown to bind to glycosaminoglycans. It has been suggested that heparan sulfate on cell surfaces
could provide specific ligand sites on endothelial cells to retain the highly diffusible inflammatory chemokine for presentation
to leukocytes. By using selectively modified heparin and heparan sulfate fragments in a nitrocellulose filter trapping system,
we have analyzed sequence requirements for interleukin-8 binding to heparin/heparan sulfate. We demonstrate that the affinity
of a monomeric interleukin-8 molecule for heparin/heparan sulfate is too weak to allow binding at physiological ionic strength,
whereas the dimeric form of the protein mediates binding to two sulfated domains of heparan sulfate. These domains, each an
N -sulfated block of â¼6 monosaccharide units, are contained within an â¼22â24-mer sequence and are separated by a region of â¤14
monosaccharide residues that may be fully N -acetylated. Binding to interleukin-8 correlates with the occurrence of the di- O -sulfated disaccharide unit -IdceA(2-OSO 3 )-GlcNSO 3 (6-OSO 3 )-. We suggest that the heparan sulfate sequence binds in horseshoe fashion over two antiparallel-oriented helical regions
on the dimeric protein. |
---|---|
ISSN: | 0021-9258 1864-6158 1864-6166 1083-351X |
DOI: | 10.1074/jbc.273.25.15487 |