Structure of human thrombospondin: complete amino acid sequence derived from cDNA

Elucidation of the complete amino acid sequence of TSP has suggested plausible explanations for all of the earlier observations on TSP structure and has already suggested new and interesting avenues of investigation aimed at determining the precise function and mechanism of TSP action as a matrix protein. The potential for Ca++-regulated exposure of the RGDA sequence could represent a new level of control for this important recognition system. We have already shown that the binding of TSP to collagen is modulated by the binding of Ca++ to this region of TSP. That is, high Ca++ results in a lower affinity of TSP for collagen, whereas lower Ca++ concentrations enhance the affinity of this interaction. The highly conserved, although short, 15-residue segment, which is nearly identical to region II of the sporozoite malaria protein, may indicate that TSP interacts with a receptor on liver cells, which the malaria parasite uses to gain its initial toehold in the body. If so, this would be another example of pathogenic organisms using a preexisting host recognition system to gain entry to cells where it can multiply. The collagen propeptide-like segment occurs in the collagen-binding domain of TSP and thus may represent the site at which TSP interacts with the collagens. These speculations form the starting point for many exciting lines of experimentation, which will provide us with a better understanding of the role of TSP in hemostasis, in the matrix of a variety of cells, and in development.