Prion proteins at interfaces : links with pathological activity
Dr , Sylvie Noinville
CNRS-Sorbonne Universités (UPMC), Laboratoire MONARIS, Paris 75005
Prion diseases belong to the growing group of disorders that are attributed to misfolding and ordered aggregation of proteins, which include Alzheimer’s disease, Parkinson’s disease and many others . The a-to-b conversion of normal PrPC to its pathological isoform PrPSc is a key event in transmissible encephalopathies. The specificity of the PrP is to adopt a wide range of conformations following chemical and physical perturbations. Surface-induced conformational changes of PrP are at the origin of accelerating fibrillation or to prevent it depending on the chemical nature of solid synthetic models or lipid bilayers, as shown by FTIR-ATR . A convergence of evidence strongly suggests that soluble oligomers or small fibrillar fragments of PrP, as on- or off-pathway products, are considered to be the most toxic species in prion diseases. Soluble discrete oligomers were obtained depending on the single mutation or truncation of the full length primary sequence, and then purified. We compare their structural properties when associated with anionic lipid bilayers and study their propensities to permeabilize the membrane. The impairments of the membrane by the soluble oligomers are correlated to their neuronal toxicities at submicromolar concentrations as shown by cell culture assays .
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3. Crosnier, S.; Beringue, V.; Rezaei, H.; Noinville, S., Membrane permeabilization and neuronal toxicities induced by PrP oligomers: essential role of the H2H3 oligomerization domain for neurotoxicity J.Biol.Chem submitted.
Date of update May 28, 2018