title: Platelet-agglutinating protein p37 from a patient with thrombotic thrombocytopenic purpura has characteristics similar to prethrombin 2.
abstract: Thrombotic thrombocytopenic purpura (TTP) is characterized by widespread platelet thrombi in arterioles and capillaries. Unusually large or multimeric von Willebrand factor, as well as one or more platelet-agglutinating factors, have been implicated in the pathogenesis of TTP. But, the actual mechanisms of platelet agglutination have not been satisfactorily explained. Recent studies suggested the 37-kDa platelet-agglutinating protein (PAP) p37 to be partially responsible for the formation of platelet thrombi in patients with TTP. We studied mobility in SDS-PAGE, the sequence of N-terminal amino acid residues, DNA and antigenic characteristics of PAP p37, which might be related to the pathogenesis of TTP. PAP p37 was purified from the plasma of a 31-year-old male Korean patient with acute TTP. The findings are as follows: (1) We compared PAP p37 with thrombin through the use of SDS-PAGE, either with or without beta-mercaptoethanol. PAP p37 did not appear to be cleaved between the A- and B-chains of prethrombin 2. However, thrombin did cleave between those of prethrombin 2, but linked with disulfide bridge. (2) N-terminal 21 amino acid sequence of PAP p37 was T-F-G-S-G- E-A-D-X-G-L-R-P-L-F-E-K-K-S-L-E. It appeared to be identical to that of 285-305 amino acid residues of human prothrombin (prethrombin 2). (3) No prothrombin gene DNA mutation was revealed. (4) The antigenicity of PAP p37 was similar to thrombin, which was a result of the competitive binding against the anti-thrombin antibody. With these results, we conclude that PAP p37 has similar characteristics to prethrombin2.
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001798:Blood Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D002847:Chromatography, Agarose; D004591:Electrophoresis, Polyacrylamide Gel; D004792:Enzyme Precursors / Q000737:chemistry* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D008623:Mercaptoethanol / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D011516:Prothrombin / Q000737:chemistry* / Q000235:genetics; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood* / Q000209:etiology; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein
chemical_list: D001798:Blood Proteins; D004792:Enzyme Precursors; C046935:platelet agglutinating protein, thrombotic thrombocytopenic purpura; D008623:Mercaptoethanol; D011516:Prothrombin; C012007:prethrombins