Tenascin-C binds heparin by its fibronectin type III domain five.
Two sites on tenascin mediate interactions with glycosaminoglycan chains of proteoglycans. One is situated on the fibrinogen-like domain, whereas the other lies within the fibronectin type III homology region (Aukhil, I., Joshi, P., Yan, Y.Z., and Erickson, H.P. (1993) J. Biol. Chem. 268, 2542-2553.). We now characterize the latter binding site more closely by means of recombinant protein fragments derived from the type III homology region of tenascin. Using a heparin-Sepharose column, we localize the second heparin binding site to the fifth fibronectin type III domain. This is confirmed in solid phase assays by incubation of fusion proteins with biotin-labeled heparin. In addition, we demonstrate the binding of heparan sulfate and dermatan sulfate to domain five. Molecular modelling of this domain reveals a conserved heparin-binding motif that we propose as the putative binding site. The fact, that different glycosaminoglycans may bind to this domain, implies that different classes of proteoglycans may in vivo compete for the same site.
Weber
P
P
Department für Pathologie, Universität Zürich, Switzerland.
Zimmermann
D R
DR
Winterhalter
K H
KH
Vaughan
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001710:Biotin; D002417:Cattle; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D004274:DNA, Recombinant; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006493:Heparin / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D012685:Sepharose / Q000031:analogs & derivatives / Q000378:metabolism; D012754:Sharks; D013552:Swine; D019063:Tenascin
D015816:Cell Adhesion Molecules, Neuronal; D004274:DNA, Recombinant; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D006025:Glycosaminoglycans; D011993:Recombinant Fusion Proteins; D019063:Tenascin; C037405:heparin-sepharose; D001710:Biotin; D006493:Heparin; D012685:Sepharose