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NMR solution structure of the peptide fragment 1-30, derived from mouse Doppel protein, in DHPC micelles
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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2006 In: Biochemistry, ISSN 0006-2960, Vol. 45, no 1, 159-166 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2006. Vol. 45, no 1, 159-166 p.
URN: urn:nbn:se:su:diva-24500OAI: diva2:197660
Part of urn:nbn:se:su:diva-7109Available from: 2007-10-04 Created: 2007-10-04Bibliographically approved
In thesis
1. Biophysical studies of membrane interacting peptides derived from viral and Prion proteins
Open this publication in new window or tab >>Biophysical studies of membrane interacting peptides derived from viral and Prion proteins
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis focuses on peptides derived from the Prion, Doppel and Influenza haemagglutinin proteins in the context of bilayer interactions with model membranes and live cells. The studies involve spectroscopic techniques like fluorescence, fluorescence correlation spectroscopy (FCS), circular and linear dichroism (CD and LD), confocal fluorescence microscopy and NMR.

The peptides derived from the Prion and Doppel proteins combined with their subsequent nuclear localization-like sequences, makes them resemble cell-penetrating peptides (CPPs). mPrPp(1-28), corresponding to the first 28 amino acids of the mouse PrP, was shown to translocate across cell membranes, concomitantly causing cell toxicity. Its bovine counterpart bPrPp(1-30) was demonstrated to enter live cells, with and without cargo, mainly via macropinocytosis. The mPrPp(23-50) peptide sequence overlaps with mPrPp(1-28) sharing the KKRPKP sequence believed to encompass the driving force behind translocation. mPrPp(23-50) was however found unable to cross over cell membranes and had virtually no perturbing effects on membranes.

mDplp(1-30), corresponding of the first 30 N-terminal amino acids of the Doppel protein, was demonstrated to be almost as membrane perturbing as melittin. NMR experiments in bicelles implied a transmembrane configuration of its alpha-helix, which was corroborated by LD in vesicle bilayers. The positioning of the induced alpha-helix in transportan was found to be more parallel to the bilayer surface in the same model system.

Positioning of the native Influenza derived fusion peptide in bilayers showed no pH dependence. The glutamic acid enriched variant however, changed its insertion angle from 70 deg to a magic angle alignment relative the membrane normal upon a pH drop from 7.4 to 5.0. Concomitantly, the alpha-helical content dramatically rose from 18% to 52% in partly anionic membranes, while the native peptide’s helicity increased only from 39% to 44% in the same conditions.

Place, publisher, year, edition, pages
Stockholm: Institutionen för biokemi och biofysik, 2007. 69 p.
Prion peptides, Doppel peptide, Influenza fusion peptides, peptide-membrane interactions, translocation, linear dichroism, circular dichroism
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urn:nbn:se:su:diva-7109 (URN)978-91-7155-502-1 (ISBN)
Public defence
2007-10-26, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 10:00
Available from: 2007-10-04 Created: 2007-10-04 Last updated: 2015-03-23Bibliographically approved

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