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Vitronectin is an abundant glycoprotein found in blood plasma and the extracellular matrix. Vitronectin has been speculated to be involved in hemostasis and tumor malignancy.
Vitronectin is a 75 kDa glycoprotein, consisting of 459 amino acid residues. About one third of the proteins molecular mass is composed of carbohydrates. Occasionally the protein is cleaved after arginine 379, to produce two chain vitronectin, where the two parts are linked by a disulfide bond. No high resolution structure has been determined experimentally yet.
The protein consists of three domains:
Several structures has been reported for the Somatomedin B domain. Initially the protein was crystallized in complex with one of its physiological binding partners: the Plasminogen activator inhibitor-1 (PAI-1), and the structure solved for this complex. Subsequently two groups reported NMR structures of the domain. The Somatomedin B domain is a close knit disulfide knot, with 4 disulfide bonds within 35 residues. Different disulfide configurations had been reported for this domain but this ambiguity has been resolved by the crystal structure.
Homology models have been built for the central and C-terminal domains.
The Somatomedin B domain of Vitronectin binds to Plasminogen activator inhibitor-1 (PAI-1), and stabilizes it. Thus vitronectin serves to regulate proteolysis initiated by plasminogen activation. Additionally vitronectin is a component of platelets and is thus involved in hemostasis. Vitronectin contains an RGD (45-47) sequence which is a binding site for membrane bound integrins, which serve to anchor cells to the extra cellular matrix. The Somatomedin B domain interacts with the urokinase receptor, and this interaction has been implicated in cell migration and signal transduction. High plasma levels of both PAI-1 and the urokinase receptor have been shown to correlate with a negative prognosis for cancer patients. Cell adhesion and migration are directly involved in cancer metastasis, which provides a probable mechanistic explanation for this observation.
Categories: Genes on chromosome 17 | Human proteins | Proteins
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Vitronectin". A list of authors is available in Wikipedia.|