PrP(106-126) does not interact with membranes under physiological conditions

Sonia T Henriques, Leonard Keith Pattenden, Marie Isabel Aguilar, Miguel A R B Castanho

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67 Citations (Scopus)

Abstract

Transmissible spongiform encephalopathies are neurodegenerative diseases with characteristic accumulation of an abnormal isoform of the prion protein, PrP(Sc). Its fragment 106-126 was reported to maintain most of the pathological features of PrP(Sc) and a role in neurodegeneration was proposed based on the modulation of membrane properties and channel formation. While the ability of PrP(Sc) to modulate membranes and/or form channels in membranes has not been clearly demonstrated, if these processes are important, peptide-membrane interactions would be a key feature to the toxicity of PrP(Sc). In the present work, the interaction of PrP(106-126) with model membranes comprising typical lipid identities as well as more specialised lipids such as phosphatidylserine and GM1 ganglioside, was examined using surface plasmon resonance and fluorescence methodologies. This comprehensive study examines different parameters relevant to characterisation of peptide-membrane interactions including: membrane charge, viscosity, lipid composition, pH and ionic strength. We report that PrP(106-126) has a low affinity for lipid membranes under physiological conditions without evidence for membrane disturbances. Membrane insertion and leakage only occurs under conditions where strong electrostatic interactions operate. These results support the hypothesis that the physiological prion protein, PrP(C), mediates PrP(106-126) toxic effects in neuronal cells.
Original languageEnglish
Pages (from-to)1877 - 1889
Number of pages13
JournalBiophysical Journal
Volume95
Issue number4
Publication statusPublished - 2008

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