Truncation of ADAMTS13 by Plasmin Enhances Its Activity in Plasma

摘要: ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) cleaves von Willebrand Factor (VWF) multimers to control their thrombogenicity. The fibrinolytic enzyme plasmin can cleave VWF in similar manner. However, also ADAMTS13, which ultimately inactivates it. This leaves the overall role of primary haemostasis uncertain. We investigated combined molecular effects on ADAMTS13. first identified that destroys FRETS-VWF73 substrate by cleaving binding region buffered system. next how affects both under static conditions plasma western blotting. found globular is largely protected from cleavage. rapidly cleaved these conditions, suggesting inactivation. Surprisingly, we observed enhances activity modified two-stage assay protects degradation. In direct studies same generates multiple C-terminally truncated forms VWF-binding capacity. an effort seek evidence for this mechanism vivo, analysed patients systemic amyloidosis, hallmarked hyperfibrinolytic state. contained increased levels correlated propose truncation abolishes intramolecular self-association, improves interaction unfolded VWF.