GgaEX0028209 @ galGal4

The proteoglycans aggrecan, versican, neurocan, and brevican bind hyaluronan through their N-terminal G1 domains, and other extracellular matrix proteins through the C-type lectin repeat in their C-terminal G3 domains. Here the authors identify tenascin-C as a ligand for the lectins of all these proteoglycans and map the binding site on the tenascin molecule to fibronectin type III repeats, which corresponds to the proteoglycan lectin-binding site on tenascin-R. In the G3 domain, the C-type lectin is flanked by two epidermal growth factor (EGF) repeats and a complement regulatory protein-like motif. In aggrecan, the EGF repeats are subject to alternative splicing (each repeat is encoded by a cassette exon: EGF-like 1 is encoded by HsaEX0001787, and EGF-like 2 is encoded by HsaEX0001788). To investigate if these flanking modules affect the C-type lectin ligand interactions, the authors produced recombinant proteins corresponding to aggrecan G3 splice variants. The G3 variant proteins containing the C-type lectin showed different affinities for various ligands, including tenascin-C, tenascin-R, fibulin-1, and fibulin-2. The presence of an EGF motif enhanced the affinity of interaction, and in particular the splice variant containing both EGF motifs had significantly higher affinity for ligands, such as tenascin-R and fibulin-2.