Repositório da Universidade de Lisboa >
Instituto de Medicina Molecular (IMM) >
IMM - Artigos em Revistas Internacionais >
Please use this identifier to cite or link to this item:
|Title: ||PrP(106-126) does not interact with membranes under physiological conditions|
|Authors: ||Henriques, Sónia Troeira|
Pattenden, Leonard Keith
Castanho, Miguel A. R. B.
|Issue Date: ||2008|
|Publisher: ||Biophysical Society|
|Citation: ||Biophysical Journal Volume 95 August 2008 1877–1889|
|Abstract: ||Transmissible spongiform encephalopathies are neurodegenerative diseases characterized by the accumulation of an abnormal isoform of the prion protein PrPSc. Its fragment 106-126 has been reported to maintain most of the pathological features of PrPSc, and a role in neurodegeneration has been proposed based on the modulation of membrane properties and channel formation. The ability of PrPSc 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 PrPSc. 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 peptidemembrane 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 PrPC mediates PrP(106-126) toxic effects in neuronal cells.|
|Description: ||© 2008 by the Biophysical Society|
|Peer Reviewed: ||yes|
|Appears in Collections:||IMM - Artigos em Revistas Internacionais|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.