Cryo-electron microscopy of coagulation Factor VIII bound to lipid nanotubes

Christopher D J Parmenter, Matthew C. Cane, Rui Zhang, Svetla Stoilova-McPhie

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Factor VIII (FVIII) is a key protein in blood coagulation, deficiency or malfunction of which causes Haemophilia A. The sole cure for this condition is intravenous administration of FVIII, whose membrane-bound structure we have studied by Cryo-electron microscopy and image analysis. Self-assembled lipid nanotubes were optimised to bind FVIII at close to native conditions. The tubes diameter was constant at 30 nm and the lipid bilayer resolved. The FVIII molecules were well defined, forming an 8.5 nm thick outer layer, and appeared to reach the hydrophobic core of the bilayer. The two known FVIII atomic models were superimposed with the averaged 2D protein densities. The insertion of the FVIII within the membrane was evaluated, reaffirming that the membrane-binding C2 or C1-C2 domain(s) fully penetrate the outer leaflet of the lipid layer. The presented results lay the basis for new models of the FVIII overall orientation and membrane-binding mechanism.

Original languageEnglish (US)
Pages (from-to)288-293
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume366
Issue number2
DOIs
StatePublished - Feb 8 2008
Externally publishedYes

Fingerprint

Cryoelectron Microscopy
Nanotubes
Factor VIII
Electron microscopy
Lipids
Membranes
Lipid bilayers
Hemophilia A
Lipid Bilayers
Blood Coagulation
Coagulation
Intravenous Administration
Image analysis
Proteins
Blood
Molecules

Keywords

  • Coagulation Factor VIII
  • Cryo-electron microscopy
  • Image analysis
  • Lipid nanotubes
  • Membrane-binding
  • Models fitting

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Cryo-electron microscopy of coagulation Factor VIII bound to lipid nanotubes. / Parmenter, Christopher D J; Cane, Matthew C.; Zhang, Rui; Stoilova-McPhie, Svetla.

In: Biochemical and Biophysical Research Communications, Vol. 366, No. 2, 08.02.2008, p. 288-293.

Research output: Contribution to journalArticle

Parmenter, Christopher D J ; Cane, Matthew C. ; Zhang, Rui ; Stoilova-McPhie, Svetla. / Cryo-electron microscopy of coagulation Factor VIII bound to lipid nanotubes. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 366, No. 2. pp. 288-293.
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