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• W4248133039 endingPage "4179" @default.
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• W4248133039 abstract "β2-Glycoprotein I (β2GPI) is a highly glycosylated plasma protein with the ability to bind negatively charged substances such as DNA, heparin, dextran sulfate, and negatively charged phospholipids. The most relevant physiological role of β2GPI is supposed to be the regulation of the function of anionic phospholipids like cardiolipin (CL). β2GPI consists of a single polypeptide chain (326 amino acid residues) with a molecular mass of about 50 kD and with five tandem repeated domains (I, II, III, IV, and V). In the previous study, we found that factor Xa can produce the nicked form by cleaving Lys 317-Thr 318, using recombinant human domain V (r-Domain V). However, the reaction was extremely slow. In the present paper, we found that plasmin can produce the nicked form of domain V, using recombinant domain V (r-Domain V) and β2GPI from human plasma. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, r-Domain V was rapidly cleaved into a nicked form by plasmin, very slowly by factor Xa, but not by thrombin, tissue-type plasminogen activator, urokinase, and tissue factor/factor VIIa. The cleavage site of r-Domain V and β2GPI by plasmin was proved to be Lys 317-Thr 318 by amino acid sequence analysis of the digest and of the C-terminal peptide isolated by high-performance liquid chromatography. The cleavage was completely inhibited by plasmin inhibitor (α2PI). The nicked form was demonstrated to show reduced affinity for CL with a dissociation constant of one order of magnitude larger than that of the intact β2GPI. To determine whether the specific cleavage of β2GPI by plasmin can occur also in plasma, human plasma was first acid-treated to inactivate α2PI and then incubated with urokinase. About 12% of β2GPI in plasma was nicked when α2PI activity decreased to 80%. The nicked form was not generated in plasminogen-depleted plasma. These results suggest that plasmin can produce the nicked form of β2GPI with the reduced ability to bind phospholipids in vivo." @default.
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• W4248133039 date "1998-06-01" @default.
• W4248133039 modified "2023-09-28" @default.
• W4248133039 title "Plasmin Can Reduce the Function of Human β2Glycoprotein I by Cleaving Domain V Into a Nicked Form" @default.
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• W4248133039 doi "https://doi.org/10.1182/blood.v91.11.4173.411k35_4173_4179" @default.
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