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Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay
Published on: September 9, 2012
Multimerin 1 binds factor V and activated factor V with high affinity and inhibits thrombin generation
Samira B Jeimy1, Nola Fuller, Subia Tasneem
1Department of Pathology and Molecular Medicine, Health Sciences Center, McMaster University, 1200 Main St. West, Hamilton, Ontario, Canada, L8N 3Z5.
Thrombosis and Haemostasis
|January 10, 2009
Summary
Multimerin 1 (MMRN1) binds factor V (FV) and its activated form (FVa) with high affinity. Exogenous MMRN1 inhibits thrombin generation, suggesting a role in regulating blood coagulation.
Area of Science:
- Biochemistry
- Hematology
- Molecular Biology
Background:
- Multimerin 1 (MMRN1) is a protein found in platelet and endothelial cell granules.
- It forms complexes with factor V (FV) within human platelet alpha-granules.
- The FV binding site on MMRN1 overlaps with membrane binding sites crucial for activated FV (FVa) function.
Purpose of the Study:
- To investigate the binding kinetics and functional consequences of factor V (FV) and activated factor V (FVa) interaction with Multimerin 1 (MMRN1).
- To elucidate the role of MMRN1 in regulating thrombin generation and FV activation.
Main Methods:
- Surface Plasmon Resonance (SPR) to measure binding affinities and kinetics.
- Circular Dichroism (CD) spectroscopy to assess conformational changes.
- Thrombin generation assays using plasma, platelets, and purified proteins.
Main Results:
- FV and FVa exhibit high-affinity binding to MMRN1 (K(D) of 2 nM and 7 nM, respectively).
- Soluble phosphatidylserine competitively inhibits FV-MMRN1 and FVa-MMRN1 binding.
- Exogenous MMRN1 delays and reduces thrombin generation and inhibits FV activation.
Conclusions:
- High-affinity binding of FV to MMRN1 facilitates their co-storage in platelet alpha-granules.
- MMRN1 release upon platelet activation may limit platelet-dependent thrombin generation in vivo.
- MMRN1 plays a regulatory role in the coagulation cascade.
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