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Extracellular Vesicle Tissue Factor Activity Assay
Published on: December 29, 2023
The dimeric structure of factor XI and zymogen activation
Yipeng Geng1, Ingrid M Verhamme, Stephen B Smith
1Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN, USA.
Blood
|March 22, 2013
Summary
Factor XI (fXI) activation requires its dimeric structure for factor XIIa (fXIIa) but not thrombin. Platelet polyphosphates (poly-P) accelerate fXI activation by both proteases, suggesting distinct activation mechanisms.
Area of Science:
- Biochemistry
- Hematology
- Molecular Biology
Background:
- Factor XI (fXI) is a zymogen crucial for blood coagulation.
- Its dimeric structure is proposed to be essential for normal activation.
- fXI activation can be mediated by factor XIIa (fXIIa) or thrombin.
Purpose of the Study:
- To investigate the role of fXI's dimeric structure in its activation by fXIIa and thrombin.
- To explore the influence of platelet polyphosphates (poly-P) on fXI activation.
- To elucidate the distinct mechanisms of fXI activation by fXIIa and thrombin.
Main Methods:
- Utilized fXI-deficient mice models for thrombosis studies.
- Investigated fXI activation kinetics in the presence of fXIIa, thrombin, and poly-P.
- Compared the activation of fXI monomers versus dimers.
Main Results:
- fXI monomers failed to reconstitute thrombosis in fXIIa-dependent models.
- Platelet polyphosphates (poly-P) significantly accelerated fXI activation by fXIIa (30-fold) and thrombin (3000-fold).
- fXI monomers were activated slower than dimers by fXIIa with poly-P, but not by thrombin or during autoactivation.
Conclusions:
- The dimeric structure of fXI is critical for activation by fXIIa, but not by thrombin.
- fXIIa and thrombin employ distinct mechanisms for fXI activation: trans-activation and cis-activation, respectively.
- Platelet poly-P plays a significant role in modulating fXI activation by both proteases.
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