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Defining the structure of membrane-bound human blood coagulation factor Va

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Stoilova-McPhie, Svetla, Parmenter, C. D. J., Segers, K., Villoutreix, B. O. and Nicolaes, G. A. F.. (2008) Defining the structure of membrane-bound human blood coagulation factor Va. Journal of Thrombosis and Haemostasis, Vol.6 (No.1). pp. 76-82. ISSN 1538-7933

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Official URL: http://dx.doi.org/10.1111/j.1538-7836.2007.02810.x

Abstract

Background: Blood coagulation factor (F) Va is the essential protein cofactor to the serine protease FXa. Factor Va stimulates the thrombin-to-prothrombin conversion by the prothrombinase complex, by at least five orders of magnitude. Factor Va binds with very high affinity to phosphatidylserine containing phospholipid membranes, which allows the visualization of its membrane-bound state by transmission electron microscopy (EM). Methods: In this paper we present an averaged three-dimensional structure of FVa molecules attached to phosphatidylserine containing lipid tubes, as determined by EM and single particle analysis. The low-resolution FVa three-dimensional structure is compared with the available atomic models for FVa. Results: The experimental data are combined with the most suitable atomic model and a membrane-bound FVaEM model is proposed that best fits the protein density defined by EM. In the FVaEM model, the C1 and C2 membrane-binding domains are juxtaposed onto the membrane surface and the model geometries indicate a deeper insertion of both C domains into the lipid bilayer than has been previously suggested. Conclusion: The present structure is a first step towards a higher-resolution experimental structure of a human FVa molecule in its membrane-bound conformation, allowing the visualization of individual domains within FVa and its association with the membrane.

Item Type: Journal Article
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > RC Internal medicine
Divisions: Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH): Blood coagulation factors, Electron microscopy, Membranes (Biology), Molecules -- Models, Particles -- Analysis
Journal or Publication Title: Journal of Thrombosis and Haemostasis
Publisher: Wiley-Blackwell Publishing Ltd.
ISSN: 1538-7933
Date: January 2008
Volume: Vol.6
Number: No.1
Number of Pages: 7
Page Range: pp. 76-82
Identification Number: DOI:10.1111/j.1538-7836.2007.02810.x
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: British Heart Foundation, Wellcome Trust (London, England), University of Warwick
Grant number: PG/04/070 (BHF), 055663/Z/98/Z (WT)
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URI: http://wrap.warwick.ac.uk/id/eprint/30820

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