Binding of recombinant human coagulation factor VIII to lipid nanotubes.
Cryo-electron microscopy has the power to visualise lipid membranes at the closest to in vivo conditions. The structure of the lipid bilayer can be well resolved and the interactions between lipid-protein and protein-protein molecules followed at the molecular level. We undertook an extended Cryo-electron microscopy study to follow the factor VIII binding to phosphatidylserine containing lipid nanotubes at different lipid composition. Obtaining well ordered tubes is required to define the factor VIII membrane-bound structure. The observed alterations in the arrangement of the protein molecules are indicative for the flexibility of the membrane-bound factor VIII. Understanding the significance of these conformational changes is essential to comprehend the function of factor VIII in coagulation and as a drug for Hemophilia A.
Parmenter
Christopher D J
CD
Imaging Suite, Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.
Stoilova-McPhie
Svetla
S
D020285:Cryoelectron Microscopy; D005169:Factor VIII / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006467:Hemophilia A / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D043942:Nanotubes / Q000737:chemistry*; D010718:Phosphatidylserines / Q000737:chemistry*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D008051:Lipid Bilayers; D010718:Phosphatidylserines; D011994:Recombinant Proteins; C078147:F8 protein, human; D005169:Factor VIII