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

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Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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