NR AKJR
AU Sanghera,N.; Pinheiro,T.J.T.
TI Binding of prion protein to lipid membranes and implications for prion conversion
QU Journal of Molecular Biology 2002 Feb 1; 315(5): 1241-56
PT journal article
AB 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.
MH 1,2-Dipalmitoylphosphatidylcholine/metabolism; Acrylamide/metabolism; Animal; Cholesterol/metabolism; Circular Dichroism; Electrostatics; Fluoresceins/metabolism; Fluorescence; Fourier Analysis; Hamsters; Hydrogen-Ion Concentration; Hydrophobicity; Kinetics; Lipid Bilayers/chemistry/metabolism; Liposomes/chemistry/*metabolism; Membrane Microdomains/chemistry/metabolism; *Mesocricetus; Models, Molecular; Phosphatidylglycerols/metabolism; Prions/*chemistry/*metabolism; Protein Binding; Protein Structure, Secondary; Spectroscopy, Fourier Transform Infrared; Sphingomyelins/metabolism; Support, Non-U.S. Gov't; Tryptophan
AD Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK
SP englisch
PO England