Characterization of a synthetic peptide that inhibits the interaction between protein S and C4b-binding protein.
Protein S is unique among the vitamin K-dependent proteins found in blood plasma because it is a cofactor rather than a zymogen of a serine protease. Instead of a trypsin-like domain, protein S contains a domain that has sequence homology with steroid binding proteins. In order to understand the function of this structural domain, peptides have been synthesized with amino acid sequences that are homologous between human protein S and rat androgen binding protein. Two peptides, corresponding to amino acids 400-407 (PINPRLDG) and 605-614 (GVQLDLDEAI) of the protein S sequence have been tested for their effects on protein S function. Neither peptide altered the clotting of bovine or human plasma. The peptide GVQLDLDEAI enhanced the anticoagulant activity of human-activated protein C in human plasma while the peptide PINPRLDG had no effect. The peptide GVQLDLDEAI was observed to inhibit the binding of protein S to C4b-binding protein in plasma, resulting in increased concentrations of free protein S. GVQLDLDEAI was also observed to enhance the disassociation of the protein S.C4b-binding protein complex when purified complex was used. Finally, C4b-binding protein was observed to bind to GVQLDLDEAI. These results suggest that the carboxyl-terminal region of protein S, which contains the sequence GVQLDLDEAI, is involved in the interaction between protein S and C4b-binding protein.
Walker
F J
FJ
American Red Cross Blood Services, Farmington, Connecticut.
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D003181:Complement C4 / Q000378:metabolism*; D003169:Complement Inactivator Proteins; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D017293:Protein S; D011951:Receptors, Complement / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid
D002352:Carrier Proteins; D003181:Complement C4; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D009842:Oligopeptides; D017293:Protein S; D011951:Receptors, Complement