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

S. Stoilova-mcphie, C. D J Parmenter, K. Segers, B. O. Villoutreix, G. A F Nicolaes

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)76-82
Number of pages7
JournalJournal of Thrombosis and Haemostasis
Volume6
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

Fingerprint

Factor Va
Membranes
Phosphatidylserines
Electron Microscopy
Lipid Bilayers
Serine Proteases
Prothrombin
Transmission Electron Microscopy
Thrombin
Phospholipids
Proteins
Lipids

Keywords

  • Coagulation factor Va
  • Electron microscopy
  • Membrane-bound structure
  • Model fitting
  • Molecular modeling
  • Single particle reconstruction

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Stoilova-mcphie, S., Parmenter, C. D. J., Segers, K., Villoutreix, B. O., & Nicolaes, G. A. F. (2008). Defining the structure of membrane-bound human blood coagulation factor Va. Journal of Thrombosis and Haemostasis, 6(1), 76-82. https://doi.org/10.1111/j.1538-7836.2007.02810.x

Defining the structure of membrane-bound human blood coagulation factor Va. / Stoilova-mcphie, S.; Parmenter, C. D J; Segers, K.; Villoutreix, B. O.; Nicolaes, G. A F.

In: Journal of Thrombosis and Haemostasis, Vol. 6, No. 1, 01.2008, p. 76-82.

Research output: Contribution to journalArticle

Stoilova-mcphie, S, Parmenter, CDJ, Segers, K, Villoutreix, BO & Nicolaes, GAF 2008, 'Defining the structure of membrane-bound human blood coagulation factor Va', Journal of Thrombosis and Haemostasis, vol. 6, no. 1, pp. 76-82. https://doi.org/10.1111/j.1538-7836.2007.02810.x
Stoilova-mcphie, S. ; Parmenter, C. D J ; Segers, K. ; Villoutreix, B. O. ; Nicolaes, G. A F. / Defining the structure of membrane-bound human blood coagulation factor Va. In: Journal of Thrombosis and Haemostasis. 2008 ; Vol. 6, No. 1. pp. 76-82.
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