The structure of human thrombospondin, an adhesive glycoprotein with multiple calcium-binding sites and homologies with several different proteins.

Abstract

Abstract. Thrombospondin is one of a class of adhesive glycoproteins that mediate cell-to-cell and cellto-matrix interactions. We have used two monoclonal antibodies to isolate cDNA clones of thrombospondin from a human endothelial cell cDNA library and have determined the complete nucleotide sequence of the coding region. Three regions of known amino acid sequence of human platelet thrombospondin confirm that the clones are authentic. Three types of repeating amino acid sequence are present in thrombospondin. The first is 57 amino acids long and shows homology with circumsporozoite protein from Plasmodium falciparum. The second is 50-60 amino acids long and shows homology with epidermal growth factor precursor. The third occurs as a continuous eightfold repeat of a 38-residue sequence; structural homology with parvalbumin and calmodulin indicates that these repots constitute the multiple calcium-binding sites of thrombospondin. The amino acid sequence arg-glyasp-ala is included in the last type 3 repeat. This sequence is probably the site for the association of thrombospondin with cells. In addition, localized homologies with procollagen, fibronectin, and von Willebrand factor are present in one region of the thrombospondin molecule.

A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis

“…The extracellular region revealed signi®cant homology to the TSP-type 1 repeats that are known to bind to several proteins including laminin, ®bronectin, heparin, sulfatide and heparin sulfate proteoglycan (Lawler and Hynes, 1986;Bornstein, 1992;Robert, 1996) (Figure 3b). The deduced protein contains ®ve TSP-type 1 repeats while TSP1 and TSP2 each contain three.…”

A Polymorphism in Thrombospondin-1 Associated with Familial Premature Coronary Artery Disease Alters Ca2+ Binding

“…The N700S polymorphism resides at position 9, where the side chain would be expected to coordinate Ca 2ϩ through water (9). However, these residues have been considered to be part of a linker region (9,18) between the third EGF-like repeat and the Ca 2ϩ -binding repeats. To test the hypothesis that the linker binds Ca 2ϩ , we generated truncations based on the disulfide bond pattern that included the linker or the linker and up to three adjacent Ca 2ϩ -binding motifs.…”

Molecular characterization of the surface of apoptotic neutrophils: Implications for functional downregulation and recognition by phagocytes

“…38 Briefly, platelets from two cytophoresis packs (generously provided by the Scottish National Blood Transfusion Service) were washed three times in HEPES buffered saline (pH 7.4) containing 5% acid citrate dextrose then resuspended in HEPES/NaCl containing 50 mM glucose prior to stimulation with thrombin (1 U/ml final). After 2 min at 378C with continuous stirring, the activity of thrombin was stopped by addition of hirudin (4 U/ml).…”