Binding Between the Integrin aXß2 (CD11c/CD18) and Heparin

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.
ORCID
https://orcid.org/0000-0003-2219-5833
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Issue Date
2007
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Terms of Use
Attribution 3.0 United States
CC BY : this license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. Credit must be given to the authors and the original work must be properly cited.
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.
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
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Elsevier
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
https://harc.rpi.edu/
Access
Open Access
CC BY — Creative Commons Attribution