Membrane perturbation effects of peptides derived from the N-termini of unprocessed prion proteins

Mazin Magzoub, Kamila Oglȩcka, Aladdin Pramanik, L. E.Göran Eriksson, Astrid Gräslund

    Research output: Contribution to journalArticle

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)126-136
    Number of pages11
    JournalBiochimica et Biophysica Acta - Biomembranes
    Volume1716
    Issue number2
    DOIs
    StatePublished - Oct 15 2005

    Fingerprint

    Membranes
    Peptides
    Melitten
    Rhodamines
    Prions
    Cell-Penetrating Peptides
    Unilamellar Liposomes
    Toxicity
    Phospholipids
    Fluorescence
    Diphenylhexatriene
    Fluorescence Spectrometry
    Protein Sorting Signals
    Circular Dichroism
    Prion Proteins
    Spectroscopy
    Polarization
    fluorexon

    Keywords

    • CD
    • FCS
    • Fluorescence
    • Membrane perturbation
    • Phospholipid vesicle
    • Prion protein

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Cell Biology

    Cite this

    Membrane perturbation effects of peptides derived from the N-termini of unprocessed prion proteins. / Magzoub, Mazin; Oglȩcka, Kamila; Pramanik, Aladdin; Eriksson, L. E.Göran; Gräslund, Astrid.

    In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1716, No. 2, 15.10.2005, p. 126-136.

    Research output: Contribution to journalArticle

    Magzoub, Mazin ; Oglȩcka, Kamila ; Pramanik, Aladdin ; Eriksson, L. E.Göran ; Gräslund, Astrid. / Membrane perturbation effects of peptides derived from the N-termini of unprocessed prion proteins. In: Biochimica et Biophysica Acta - Biomembranes. 2005 ; Vol. 1716, No. 2. pp. 126-136.
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