Binding between the integrin αXβ2 (CD11c/CD18) and heparin

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 αXβ2 (p150,95, CD11c/CD18). Here, we analyze the structural motifs within heparin that constitute high affinity binding sites for the I domain of integrin αXβ2. Heparin oligomers with chain lengths of 10 saccharide residues or higher provide strong inhibition of the binding by the αX 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 μM affinity for the αXI domain. In studies of direct binding by the αX I domain to immobilized heparin, we found that the interaction is conformationally regulated and requires Mg ²⁺. Furthermore, the fully sulfated heparin fragment induced conformational change in the ectodomain of the αXβ2 receptor, also demonstrating allosteric linkage between heparin binding and integrin conformation.