Tenascin-C Binds Heparin by Its Fibronectin Type III Domain Five (*)
- From the Laboratorium für Biochemie I, Universitätstr. 16, ETH Zentrum, 8092 Zürich and the
- (1) Institut für klinische Pathologie, Department für Pathologie, Universität Zürich, 8091 Zürich, Switzerland
- § To whom correspondence should be addressed. Tel.: 41-632-25-72; Fax: 41-632-11-21; l_vaughan{at}ezinfo.vmsmail.ethz.ch
Abstract
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.
Footnotes
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↵* This work was supported by grants from the Swiss National Science Foundation and the ETH-Zürich (to L. V.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- TNfn
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fibronectin type III homology domain of tenascin
- ECM
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extracellular matrix
- TNfbg
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fibrinogen like domain of tenascin
- HS
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heparan sulfate
- GAG
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glycosaminoglycan
- TBS
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Tris-buffered saline.
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↵2P. Weber and L. Vaughan, unpublished observations.
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- Received October 20, 1994.
- Revision received December 22, 1994.
