title: Binding of prion protein to lipid membranes and implications for prion conversion.
abstract: The binding of the Syrian hamster prion protein, SHaPrP(90-231), to model lipid membranes was investigated by tryptophan fluorescence. Membranes composed of negatively charged or zwitterionic lipids, and raft-like membranes containing dipalmitoylphosphatidylcholine(1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol and sphingomyelin, were investigated. It was found that SHaPrP(90-231) binds to negatively charged lipid membranes and raft-like membranes. Binding of PrP to negatively charged lipid membranes involves both electrostatic and hydrophobic lipid-protein interactions and results in partial insertion of PrP into the lipid bilayer. This membrane-inserted conformation of PrP is richer in beta-sheet structure and has a disruptive effect on the integrity of the lipid bilayer, leading to total release of vesicle contents. In contrast, the binding of PrP to raft-like membranes is driven by hydrophobic lipid-protein interactions and induces the formation of alpha-helical structure. This conformation of PrP with a high content of alpha-helix is formed only at pH 7 and does not destabilize the lipid bilayer. Our findings support the view that an interaction of PrP with lipid membranes could play a role in PrP conversion.
authors.affiliation: Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK.
authors.forename: Narinder
authors.initials: N
authors.lastname: Sanghera
authors.forename: Teresa J T
authors.initials: TJ
authors.lastname: Pinheiro
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D020106:Acrylamide / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D002942:Circular Dichroism; D006224:Cricetinae; D005452:Fluoresceins / Q000378:metabolism; D005453:Fluorescence; D005583:Fourier Analysis; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism; D008647:Mesocricetus; D008958:Models, Molecular; D010715:Phosphatidylglycerols / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013109:Sphingomyelins / Q000378:metabolism; D055672:Static Electricity; D014364:Tryptophan
chemical_list: D005452:Fluoresceins; D008051:Lipid Bilayers; D008081:Liposomes; D010715:Phosphatidylglycerols; D011328:Prions; D013109:Sphingomyelins; D020106:Acrylamide; D015060:1,2-Dipalmitoylphosphatidylcholine; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; D014364:Tryptophan; D002784:Cholesterol; C007740:fluorexon