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Relevance of the N-...
Relevance of the N-terminal NLS-like sequence of the prion protein for membrane perturbation effects
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- Oglęcka, Kamila (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Lundberg, Pontus (author)
- Stockholms universitet,Institutionen för neurokemi
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- Magzoub, Mazin (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Eriksson, L. E. Göran (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Langel, Ülo (author)
- Stockholms universitet,Institutionen för neurokemi
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- Gräslund, Astrid (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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(creator_code:org_t)
- Elsevier BV, 2008
- 2008
- English.
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In: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434 .- 0005-2736. ; 1778:1, s. 206-213
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- prion protein
- membrane translocation
- calcein leakage
- endosomal escape
- NLS-like sequence
- haemoglobin leakage
Publication and Content Type
- ref (subject category)
- art (subject category)
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