NR ATTX
AU Magzoub,M.; Oglecka,K.; Pramanik,A.; Eriksson,L.E.G.; Gräslund,A.
TI Membrane perturbation effects of peptides derived from the N-termini of unprocessed prion proteins
QU Biochimica et Biophysica Acta - Biomembranes 2005 Oct 15; 1716(2): 126-36
PT journal article
AB Peptides derived from the unprocessed N-termini of mouse and bovine prion proteins (mPrPp and bPrPp, respectively), comprising hydrophobic signal sequences followed by charged domains (KKRPKP), function as cell-penetrating peptides (CPPs) with live cells, concomitantly causing toxicity. Using steady-state fluorescence techniques, including calcein leakage and polarization of a membrane probe (diphenylhexatriene, DPH), as well as circular dichroism, we studied the membrane interactions of the peptides with large unilamellar phospholipid vesicles (LUVs), generally with a 30% negative surface charged density, comparing the effects with those of the CPP penetratin (pAntp) and the pore-forming peptide melittin. The prion peptides caused significant calcein leakage from LUVs concomitant with increased membrane ordering. Fluorescence correlation spectroscopy (FCS) studies of either rhodamine-entrapping (REVs) or rhodamine-labeled (RLVs) vesicles, showed that addition of the prion peptides resulted in significant release of rhodamine from the REVs without affecting the overall integrity of the RLVs. The membrane leakage effects due to the peptides had the following order of potency: melittin>mPrPp>bPrPp>pAntp. The membrane perturbation effects of the N-terminal prion peptides suggest that they form transient pores (similar to melittin) causing toxicity in parallel with their cellular trafficking.
MH Animals; Biophysics/methods; Carrier Proteins/chemistry; Cattle; Cell Membrane/*chemistry/metabolism; Circular Dichroism; Diffusion; Diphenylhexatriene/chemistry; Fluoresceins/chemistry; Melitten/chemistry; Mice; Peptides/chemistry; Prions/*chemistry; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Research Support, Non-U.S. Gov't; Rhodamines/chemistry; Spectrometry, Fluorescence; Spectrophotometry; Time Factors
AD Mazin Magzoub, Kamila Ogl?cka, L.E. Göran Eriksson, Astrid Gräslund, Department of Biochemistry and Biophysics, The Arrhenius Laboratories, Stockholm University, S-106 91 Stockholm, Sweden; Aladdin Pramanik, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-171 77 Stockholm, Sweden
SP englisch
PO Niederlande