Relevance of the N-terminal NLS-like sequence for membrane interactions of the Prion protein
2007 (English)In: Biochimica et Biophysica Acta. MR. Reviews on Biomembranes, ISSN 0304-4157, Vol. 1778, no 1, 206-213 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2007. Vol. 1778, no 1, 206-213 p.
Prion protein, Membrane translocation, Calcein leakage, Endosomal escape, NLS-like sequence, Haemoglobin leakage
Other Basic Medicine
IdentifiersURN: urn:nbn:se:su:diva-24501DOI: 10.1016/j.bbamem.2007.09.034OAI: oai:DiVA.org:su-24501DiVA: diva2:197661
Part of urn:nbn:se:su:diva-71092007-10-042007-10-042015-04-21Bibliographically approved