Common evolutionary origin of the fibrin-binding structures of fibronectin and tissue-type plasminogen activator.
Comparison of the primary structures of high-Mr urokinase and tissue-type plasminogen activator reveals a high degree of structural homology between the two proteins, except that tissue activator contains a 43 residue long amino-terminal region, which has no counterpart in urokinase. We show that this segment is homologous with the finger-domains responsible for the fibrin-affinity of fibronectin. Limited proteolysis of the amino-terminal region of plasminogen activator was found to lead to a loss of the fibrin-affinity of the enzyme. It is suggested that the finger-domains of fibronectin and tissue-types plasminogen activator have similar functions and that the finger-domains of the two proteins evolved from a common ancestral fibrin-binding domain.
D000595:Amino Acid Sequence; D005075:Biological Evolution; D002460:Cell Line; D004220:Disulfides / Q000032:analysis; D005337:Fibrin / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008545:Melanoma; D008970:Molecular Weight; D010446:Peptide Fragments / Q000032:analysis; D010960:Plasminogen Activators / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D004220:Disulfides; D005353:Fibronectins; D010446:Peptide Fragments; D005337:Fibrin; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator