Identification of the MMRN1 binding region within the C2 domain of human factor V
Författare
Summary, in English
In platelets, coagulation cofactor V is stored in complex with multimerin 1 in alpha-granules for activation- induced release during clot formation. The molecular nature of multimerin 1 factor V binding has not been determined, although multimerin 1 is known to interact with the factor V light chain. We investigated the region in factor V important for multimerin 1 binding using modified enzyme-linked immunoassays and recombinant factor V constructs. Factor V constructs lacking the C2 region or entire light chain had impaired and absent multimerin 1 binding, respectively, whereas the B domain deleted construct had modestly reduced binding. Analyses of point mutated constructs indicated that the multimerin 1 binding site in the C2 domain of factor V partially overlaps the phosphatidylserine binding site and that the factor V B domain enhances multimerin 1 binding. Multimerin 1 did not inhibit factor V phosphatidylserine binding, and it bound to phosphatidylserine independently of factor V. There was a reduction in factor V in complex with multimerin 1 after activation, and thrombin cleavage significantly reduced factor V binding to multimerin 1. In molar excess, multimerin 1 minimally reduced factor V procoagulant activity in prothrombinase assays and only if it was added before factor V activation. The dissociation of factor V-multimerin 1 complexes following factor V activation suggests a role for multimerin 1 in delivering and localizing factor V onto platelets prior to prothrombinase assembly.
Avdelning/ar
Publiceringsår
2004
Språk
Engelska
Sidor
51466-51471
Publikation/Tidskrift/Serie
Journal of Biological Chemistry
Volym
279
Issue
49
Dokumenttyp
Artikel i tidskrift
Förlag
American Society for Biochemistry and Molecular Biology
Ämne
- Medicinal Chemistry
Status
Published
Forskningsgrupp
- Clinical Chemistry, Malmö
ISBN/ISSN/Övrigt
- ISSN: 1083-351X