Novel heparin-binding site in tenascin-C and its implication in cell adhesion

초록

Tenascin-C (TN) is a large extracellular matrix (ECM) glycoprotein composed of a linear arrangement of domains homologous to epidermal growth factor, fibronectin type III domains (FNIII), and fibrinogen. Heparin/HS binding seems to be a common feature of ECM molecules including TN; TN binds to heparin at physiological salt concentrations, although the affinity of TN binding to heparin has not been specifically demonstrated until now. The present study was undertaken to examine more specifically the interaction of TN with heparin using SPR and to delineate the putative heparin-binding site that mediates this interaction. Until today, the characterization of binding sites on heparin that interact with the FNIII domains has largely focused on the TNIII5 domain, although it is not clear whether or not these are the only motifs required for heparin interaction. In this study we investigate the specific role of the TNIII4 domain in heparin binding by characterizing wild-type and mutant TNIII proteins by the use of SPR direct binding studies. Here we present evidences suggesting that secondary heparin-binding site in TNIII4 contributes to overall TNIII binding to heparin.