Defining the interleukin-8-binding domain of heparan sulfate
1998 (English)In: Journal of chemical biology, ISSN 1864-6158, Vol. 273, no 25, 15487-15493 p.Article in journal (Refereed) Published
Interleukin-8, a member of the CXC 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 :In N-sulfated block of similar to 6 monosaccharide units, are contained within an similar to 22-24-mer sequence and are separated by a region of less than or equal to 14 monosaccharide residues that may be fully N-acetylated. Binding to interleukin-8 correlates with the occurrence of the di-O-sulfated disaccharide unit -Id-ceA(2-OSO3)-GlcNSO(3)(6-OSO3)-. We suggest that the heparan sulfate sequence binds in horseshoe fashion over two antiparallel-oriented helical regions on the dimeric protein.
Place, publisher, year, edition, pages
1998. Vol. 273, no 25, 15487-15493 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-52570DOI: 10.1074/jbc.273.25.15487OAI: oai:DiVA.org:uu-52570DiVA: diva2:80480