title: Insight into early events in the aggregation of the prion protein on lipid membranes.
abstract: The key molecular event underlying prion diseases is the conversion of the monomeric and alpha-helical cellular form of the prion protein (PrP(C)) to the disease-associated state, which is aggregated and rich in beta-sheet (PrP(Sc)). The molecular details associated with the conversion of PrP(C) into PrP(Sc) are not fully understood. The prion protein is attached to the cell membrane via a GPI lipid anchor and evidence suggests that the lipid environment plays an important role in prion conversion and propagation. We have previously shown that the interaction of the prion protein with anionic lipid membranes induces beta-sheet structure and promotes prion aggregation, whereas zwitterionic membranes stabilize the alpha-helical form of the protein. Here, we report on the interaction of recombinant sheep prion protein with planar lipid membranes in real-time, using dual polarization interferometry (DPI). Using this technique, the simultaneous evaluation of multiple physical properties of PrP layers on membranes was achieved. The deposition of prion on membranes of POPC and POPC/POPS mixtures was studied. The properties of the resulting protein layers were found to depend on the lipid composition of the membranes. Denser and thicker protein deposits formed on lipid membranes containing POPS compared to those formed on POPC. DPI thus provides a further insight on the organization of PrP at the surface of lipid membranes.
authors.affiliation: Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Narinder
authors.initials: N
authors.lastname: Sanghera
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Swann
authors.forename: Gerry
authors.initials: G
authors.lastname: Ronan
authors.forename: Teresa J T
authors.initials: TJ
authors.lastname: Pinheiro
mesh_terms: D000818:Animals; D002942:Circular Dichroism; D008051:Lipid Bilayers; D008563:Membrane Lipids / Q000378:metabolism*; D018621:PrPC Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012756:Sheep; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D008051:Lipid Bilayers; D008563:Membrane Lipids; D018621:PrPC Proteins; D011994:Recombinant Proteins