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Cryo-electron microscopy of coagulation Factor VIII bound to lipid nanotubes
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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, Volume 366 (Number 2). pp. 288-293. doi:10.1016/j.bbrc.2007.11.072
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Official URL: http://dx.doi.org/10.1016/j.bbrc.2007.11.072
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 | ||||
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| Subjects: | Q Science > QC Physics Q Science > QD Chemistry Q Science > QP Physiology |
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| Divisions: | Faculty of Science > Chemistry | ||||
| Library of Congress Subject Headings (LCSH): | Electron microscopy, Nanotubes, Blood coagulation factors, Membranes, Image analysis | ||||
| Journal or Publication Title: | Biochemical and Biophysical Research Communications | ||||
| Publisher: | Academic Press | ||||
| ISSN: | 0006-291X | ||||
| Official Date: | 8 February 2008 | ||||
| Dates: |
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| Volume: | Volume 366 | ||||
| Number: | Number 2 | ||||
| Number of Pages: | 6 | ||||
| Page Range: | pp. 288-293 | ||||
| DOI: | 10.1016/j.bbrc.2007.11.072 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | British Heart Foundation, Wellcome Trust (London, England), Robert A. Welch Foundation | ||||
| Grant number: | PG/04/070 (BHF), 055663/Z/98/Z (WT) |
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