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

Abstract:

:Transmissible spongiform encephalopathies are neurodegenerative diseases characterized by the accumulation of an abnormal isoform of the prion protein PrP(Sc). Its fragment 106-126 has been reported to maintain most of the pathological features of PrP(Sc), and a role in neurodegeneration has been proposed based on the modulation of membrane properties and channel formation. The ability of PrP(Sc) to modulate membranes and/or form channels in membranes has not been clearly demonstrated; however, if these processes are important, peptide-membrane interactions would be a key feature in the toxicity of PrP(Sc). In this work, the interaction of PrP(106-126) with model membranes comprising typical lipid identities, as well as more specialized lipids such as phosphatidylserine and GM1 ganglioside, was examined using surface plasmon resonance and fluorescence methodologies. This comprehensive study examines different parameters relevant to characterization 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 of membrane disturbances. Membrane insertion and leakage occur only under conditions in which 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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Henriques ST,Pattenden LK,Aguilar MI,Castanho MA

doi

10.1529/biophysj.108.131458

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

1877-89

issue

4

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(08)70147-4

journal_volume

95

pub_type

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