Structure and Function of Thrombospondins

Abstract

The thrombospondins(TS) are a family of proteins which appear to be involved in the acute regulation of the migration, adhesion and proliferation of a number of cell types. The proteins consist of modular domains, at least four of which contain cellular binding sites. One of these sites in the amino terminal heparin binding domain binds heparin and similar sulfated glycans. The three other sites reside in linear peptide sequences. One of these is the RGDA sequence within the calcium binding domain. A second site was recently identified in the properdin-like repeats of TS and contains the sequnce CSVTCG. This appears to be a “compound” adhesive site in that it is immediately followed by a cluster of positively charged amino acids that may bind sulfated glycans, and is preceded by a WXXWXXW motif conserved in several homologues of TS. The C terminal domain of TS appears to contain another cell adhesive site that is independent of the nearby RGD sequence. The binding of cells to this C terminal peptide site may be augmented by a nearby heparin binding site as well. Receptors have been tentatively identified for all of these sites.