title: Binding between the integrin alphaXbeta2 (CD11c/CD18) and heparin.
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.
authors: Immune Disease Institute (formerly CBR Institute for Biomedical Research), Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Thomas
authors: T
authors: Vorup-Jensen
authors: Lianli
authors: L
authors: Chi
authors: Louise C
authors: LC
authors: Gjelstrup
authors: Uffe B
authors: UB
authors: Jensen
authors: Craig A
authors: CA
authors: Jewett
authors: Can
authors: C
authors: Xie
authors: Motomu
authors: M
authors: Shimaoka
authors: Robert J
authors: RJ
authors: Linhardt
authors: Timothy A
authors: TA
authors: Springer
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology; D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D039521:CD11c Antigen / Q000737:chemistry* / Q000378:metabolism; D018821:CD18 Antigens / Q000737:chemistry* / Q000378:metabolism; D002417:Cattle; D002448:Cell Adhesion / Q000502:physiology; D003179:Complement C3b / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006493:Heparin / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008274:Magnesium / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship; D014574:Uronic Acids / Q000737:chemistry / Q000378:metabolism
chemical_list: D039521:CD11c Antigen; D018821:CD18 Antigens; D011994:Recombinant Proteins; D014574:Uronic Acids; D003179:Complement C3b; D006493:Heparin; D008274:Magnesium
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