title: Membrane environment alters the conformational structure of the recombinant human prion protein.
abstract: The prion protein (PrP) in a living cell is associated with cellular membranes. However, all previous biophysical studies with the recombinant prion protein have been performed in an aqueous solution. To determine the effect of a membrane environment on the conformational structure of PrP, we studied the interaction of the recombinant human prion protein with model lipid membranes. The protein was found to bind to acidic lipid-containing membrane vesicles. This interaction is pH-dependent and becomes particularly strong under acidic conditions. Spectroscopic data show that membrane binding of PrP results in a significant ordering of the N-terminal part of the molecule. The folded C-terminal domain, on the other hand, becomes destabilized upon binding to the membrane surface, especially at low pH. Overall, these results show that the conformational structure and stability of the recombinant human PrP in a membrane environment are substantially different from those of the free protein in solution. These observations have important implications for understanding the mechanism of the conversion between the normal (PrP(C)) and pathogenic (PrP(Sc)) forms of prion protein.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: M
authors.initials: M
authors.lastname: Morillas
authors.forename: W
authors.initials: W
authors.lastname: Swietnicki
authors.forename: P
authors.initials: P
authors.lastname: Gambetti
authors.forename: W K
authors.initials: WK
authors.lastname: Surewicz
mesh_terms: D002462:Cell Membrane / Q000737:chemistry; D002942:Circular Dichroism; D005453:Fluorescence; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D011328:Prions; D011994:Recombinant Proteins