PMID: 19132231Jan 10, 2009Paper

Multimerin 1 binds factor V and activated factor V with high affinity and inhibits thrombin generation

Thrombosis and Haemostasis
Samira B JeimyC P Hayward

Abstract

Multimerin 1 (MMRN1) is a polymeric, factor V (FV) binding protein that is stored in platelet and endothelial cell secretion granules but is undetectable in normal plasma. In human platelet alpha-granules, FV is stored complexed to MMRN1, predominantly by noncovalent binding interactions. The FV binding site for MMRN1 is located in the light chain, where it overlaps the C1 and C2 domain membrane binding sites essential for activated FV (FVa) procoagulant function. Surface plasmon resonance (SPR), circular dichroism (CD) and thrombin generation assays were used to study the binding of FV and FVa to MMRN1, and the functional consequences. FV and FVa bound MMRN1 with high affinities (K(D): 2 and 7 nM, respectively). FV dissociated more slowly from MMRN1 than FVa in SPR experiments, and CD analyses suggested greater conformational changes in mixtures of FV and MMRN1 than in mixtures of FVa and MMRN1. SPR analyses indicated that soluble phosphatidylserine (1,2-Dicaproylsn-glycero-3-phospho-L-serine) competitively inhibited both FV-MMRN1 and FVa-MMRN1 binding. Furthermore, exogenous MMRN1 delayed and reduced thrombin generation by plasma and platelets, and it reduced thrombin generation by preformed FVa. Exogenous MMRN1 also delayed ...Continue Reading

Citations

Dec 26, 2009·Genome Medicine·Sharon J PitteriRoss L Prentice
Jan 30, 2009·Journal of Thrombosis and Haemostasis : JTH·S TasneemC P M Hayward
Dec 18, 2009·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
May 20, 2009·Blood Reviews·Price Blair, Robert Flaumenhaft
Jul 4, 2016·Trends in Pharmacological Sciences·Bruno O Villoutreix, Maria A Miteva
Mar 29, 2014·Circulation Research·Bruce Furie, Robert Flaumenhaft
Nov 1, 2011·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Georgia AnastasiouAnthi Travlou
Apr 8, 2016·Thrombosis and Haemostasis·D'Andra N ParkerCatherine P M Hayward

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