Interaction of Fibronectin with Thrompospondins

Thrombospondins are a family of multimeric modular glycoproteins with a high avidity for Ca²⁺[schematic]. They are secreted into the extracellular matrix where they regulate cell growth and migration and play a role in angiogenesis [ref]. Tsp-1 is an ~ 420 kD trimer that binds integrins, matrix metallo proteinase-2 (MMP-2 ), transforming growth factor TGF-b1, proteoglycans and Fn.

At least two regions which may be cryptic within TSP appear able to bind Fn with submicromolar K_ds [ref]. The binding site on Fn has not been firmly established. Although some early work implicated the N-terminal Fib-1 region [ref], more recent studies have favored the gelatin-binding region. A peptide derived from the properdin repeats of Tsp-1, namely GGWSHW, was able to inhibit the binding of Fn to gelatin, and plastic surfaces coated with GGWSHW were able to bind Fn and a 30kDa gelatin-binding fragment but not other fragments [ref]. Yeast two-hybrid screening experiments with MMP-2 identified a TSP binding site in a region of MMP-2 that contains Fn type II modules homologous to those found in the gelatin-binding region of Fn [ref]. These data suggests that this region of Fn should be carefully considered as a potential binding site for TSP-1. Binding of Fn to TSP-1 was reported to expose a cryptic epitope in TSP-1 and to mediate its association with integrins on some cell types [ref].