Relevance of the N-terminal NLS-like sequence of the prion protein for membrane perturbation effects

Kamila Oglecka, Pontus Lundberg, Mazin Magzoub, L. E. Göran Eriksson, Ülo Langel, Astrid Gräslund

Research output: Contribution to journalArticlepeer-review


We investigated the nuclear localization-like sequence KKRPKP, corresponding to the residues 23-28 in the mouse prion protein (mPrP), for its membrane perturbation activity, by comparing effects of two mPrP-derived peptides, corresponding to residues 1-28 (mPrPp(1-28)) and 23-50 (mPrPp(23-50)), respectively. In erythrocytes, mPrPp(1-28) induced ∼ 60% haemoglobin leakage after 30 min, whereas mPrPp(23-50) had negligible effects. In calcein-entrapping, large unilamellar vesicles (LUVs), similar results were obtained. Cytotoxicity estimated by lactate dehydrogenase leakage from HeLa cells, was found to be ∼ 12% for 50 μM mPrPp(1-28), and ∼ 1% for 50 μM mPrPp(23-50). Circular dichroism spectra showed structure induction of mPrPp(1-28) in the presence of POPC:POPG (4:1) and POPC LUVs, while mPrPp(23-50) remained a random coil. Membrane translocation studies on live HeLa cells showed mPrPp(1-28) co-localizing with dextran, suggesting fluid-phase endocytosis, whereas mPrPp(23-50) hardly translocated at all. We conclude that the KKRPKP-sequence is not sufficient to cause membrane perturbation or translocation but needs a hydrophobic counterpart.

Original languageEnglish (US)
Pages (from-to)206-213
Number of pages8
JournalBiochimica et Biophysica Acta - Biomembranes
Issue number1
StatePublished - Jan 2008


  • Calcein leakage
  • Endosomal escape
  • Haemoglobin leakage
  • Membrane translocation
  • NLS-like sequence
  • Prion protein

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology


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