Binding Between the Integrin aXß2 (CD11c/CD18) and Heparin
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Authors
Vorup-Jensen, T.
Chi, L.
Gjelstrup, L.C.
Jensen, U.B.
Jewett, C.A.
Xie, C.
Shimaoka, M.
Linhardt, Robert J.
Springer, T.A.
Issue Date
2007
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
The interactions between cell surface receptors and sulfated glucosamineglycans serve ubiquitous roles in cell adhesion and receptor signaling. Heparin, a highly sulfated polymer of uronic acids and glucosamine, binds strongly to the integrin receptor alphaXbeta2 (p150,95, CD11c/CD18). Here, we analyze the structural motifs within heparin that constitute high affinity binding sites for the I domain of integrin alphaXbeta2. Heparin oligomers with chain lengths of 10 saccharide residues or higher provide strong inhibition of the binding by the alphaX I domain to the complement fragment iC3b. By contrast, smaller oligomers or the synthetic heparinoid fondaparinux were not able to block the binding. Semipurified heparin oligomers with 12 saccharide residues identified the fully sulfated species as the most potent antagonist of iC3b, with a 1.3 microM affinity for the alphaX I domain. In studies of direct binding by the alphaX I domain to immobilized heparin, we found that the interaction is conformationally regulated and requires Mg2+. Furthermore, the fully sulfated heparin fragment induced conformational change in the ectodomain of the alphaXbeta2 receptor, also demonstrating allosteric linkage between heparin binding and integrin conformation.
Description
Journal of Biological Chemistry, 282, 30869-30877
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Binding Between the Integrin aXß2 (CD11c/CD18) and Heparin, T. Vorup-Jensen, L. Chi, L. C. Gjelstrup, U. B. Jensen, C. A. Jewett, C. Xie, M. Shimaoka, R. J. Linhardt, T. A. Springer, Journal of Biological Chemistry, 282, 30869-30877, 2007.
Publisher
Elsevier