Parmenter, Christopher D. J., Cane, Matthew C., Zhang, Rui and Stollova-McPhie, Svetla. (2008) Cryo-electron microscopy of coagulation Factor VIII bound to lipid nanotubes. Biochemical and Biophysical Research Communications, Vol.366 (No.2). pp. 288-293. ISSN 0006-291X

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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. (C) 2007 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology
Divisions:	Faculty of Science > Chemistry
Journal or Publication Title:	Biochemical and Biophysical Research Communications
Publisher:	Academic Press
ISSN:	0006-291X
Date:	8 February 2008
Volume:	Vol.366
Number:	No.2
Number of Pages:	6
Page Range:	pp. 288-293
Identification Number:	10.1016/j.bbrc.2007.11.072
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
URI:	http://wrap.warwick.ac.uk/id/eprint/30771

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