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Identification of the MMRN1 binding region within the C2 domain of human factor V

Jeimy, SB; Woram, RA; Fuller, N; Quinn-Allen, MA; Nicolaes, GAF; Dahlbäck, Björn LU ; Kane, WH and Hayward, CPM (2004) In Journal of Biological Chemistry 279(49). p.51466-51471
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
279
issue
49
pages
51466 - 51471
publisher
ASBMB
external identifiers
  • wos:000225355800099
  • scopus:10944220793
ISSN
1083-351X
DOI
10.1074/jbc.M409866200
language
English
LU publication?
yes
id
b5fc8bc6-23ff-42fc-be60-5b175a00bcc4 (old id 260111)
date added to LUP
2007-10-23 11:42:18
date last changed
2017-01-01 05:01:14
@article{b5fc8bc6-23ff-42fc-be60-5b175a00bcc4,
  abstract     = {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.},
  author       = {Jeimy, SB and Woram, RA and Fuller, N and Quinn-Allen, MA and Nicolaes, GAF and Dahlbäck, Björn and Kane, WH and Hayward, CPM},
  issn         = {1083-351X},
  language     = {eng},
  number       = {49},
  pages        = {51466--51471},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Identification of the MMRN1 binding region within the C2 domain of human factor V},
  url          = {http://dx.doi.org/10.1074/jbc.M409866200},
  volume       = {279},
  year         = {2004},
}