Identification of the MMRN1 binding region within the C2 domain of human factor V
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/260111
- author
- Jeimy, SB ; Woram, RA ; Fuller, N ; Quinn-Allen, MA ; Nicolaes, GAF ; Dahlbäck, Björn LU ; Kane, WH and Hayward, CPM
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 279
- issue
- 49
- pages
- 51466 - 51471
- publisher
- American Society for Biochemistry and Molecular Biology
- 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
- 2016-04-01 12:17:56
- date last changed
- 2022-01-27 01:39:39
@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 = {{American Society for Biochemistry and Molecular Biology}},
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}},
doi = {{10.1074/jbc.M409866200}},
volume = {{279}},
year = {{2004}},
}