Mapping of a defined neurocan binding site to distinct domains of tenascin-C.
Neurocan is a member of the aggrecan family of proteoglycans which are characterized by NH2-terminal domains binding hyaluronan, and COOH-terminal domains containing C-type lectin-like modules. To detect and enhance the affinity for complementary ligands of neurocan, the COOH-terminal neurocan domain was fused with the NH2-terminal region of tenascin-C, which contains ... the hexamerization domain of this extracellular matrix glycoprotein. The fusion protein was designed to contain the last downstream glycosaminoglycan attachment site and was expressed as a proteoglycan. In ligand overlay blots carried out with brain extracts, it recognized tenascin-C. The interaction was abolished by the addition of EDTA, or TNfn4,5, a bacterially expressed tenascin-C fragment comprising the fourth and fifth fibronectin type III module. The fusion protein directly reacted with this fragment in ligand blot and enzyme-linked immunosorbent assay procedures. Both tenascin-C and TNfn4,5 were retained on Sepharose 4B-linked carboxyl-terminal neurocan domains, which in BIAcore binding studies yielded a KD value of 17 nM for purified tenascin-C. We conclude that a divalent cation-dependent interaction between the COOH-terminal domain of neurocan and those fibronectin type III repeats is substantially involved in the binding of neurocan to tenascin-C.
Mesh Terms:
Amino Acid Sequence, Animals, Antibodies, Monoclonal, Binding Sites, Binding, Competitive, Brain, Cell Line, Chickens, Chromatography, Affinity, Edetic Acid, Humans, Immunoblotting, Lectins, C-Type, Ligands, Mice, Models, Structural, Molecular Sequence Data, Nerve Tissue Proteins, Peptide Fragments, Protein Conformation, Proteochondroitin Sulfates, Rats, Recombinant Fusion Proteins, Recombinant Proteins, Tenascin
Amino Acid Sequence, Animals, Antibodies, Monoclonal, Binding Sites, Binding, Competitive, Brain, Cell Line, Chickens, Chromatography, Affinity, Edetic Acid, Humans, Immunoblotting, Lectins, C-Type, Ligands, Mice, Models, Structural, Molecular Sequence Data, Nerve Tissue Proteins, Peptide Fragments, Protein Conformation, Proteochondroitin Sulfates, Rats, Recombinant Fusion Proteins, Recombinant Proteins, Tenascin
J. Biol. Chem.
Date: Oct. 24, 1997
PubMed ID: 9341124
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