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Relevance of the N-terminal NLS-like sequence of the prion protein for membrane perturbation effects
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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2008 (English)In: Biochimica et Biophysica Acta, ISSN 0006-3002, Vol. 1778, no 1, 206-213 p.Article in journal (Refereed) Published
Abstract [en]

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 2350 (rnPrPp(23-50)), respectively. In erythrocytes, mPrPp(1-28) induced similar to 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 similar to 12% for 50 mu M mPrPp(1-28), and similar to 1% for 50 mu M 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(I-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.

Place, publisher, year, edition, pages
2008. Vol. 1778, no 1, 206-213 p.
Keyword [en]
prion protein, membrane translocation, calcein leakage, endosomal escape, NLS-like sequence, haemoglobin leakage
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-20657DOI: 10.1016/j.bbamem.2007.09.034ISI: 000253269500022PubMedID: 17967411OAI: oai:DiVA.org:su-20657DiVA: diva2:187183
Available from: 2008-01-23 Created: 2008-01-23 Last updated: 2015-04-21Bibliographically approved

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Eriksson, L. E. GöranLangel, ÜloGräslund, Astrid
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