TY - JOUR
T1 - The toxicity of prion protein fragment PrP(106-126) is not mediated by membrane permeabilization as shown by a M112W substitution
AU - Henriques, Sonia Troeira
AU - Pattenden, Leonard Keith
AU - Aguilar, Marie-Isabel
AU - Castanho, Miguel A R B
PY - 2009
Y1 - 2009
N2 - Prion diseases result from a post-translational modification of the physiological Prion protein (PrPC) into a scrapie isoform (PrPSc). The PrP(106-126) fragment is conserved among various abnormal variants and shows PrPSc pathogenic properties. It has been proposed that the PrP(106-126) fragment may exhibit its toxic effects through membrane channel formation. However our previous studies showed that PrP(106-126) does not interact with membranes under physiological conditions. In the present study, PrP(106-126) affinity for membranes was increased by modifying PrP(106-126) with a M112W substitution and pore formation was further evaluated. However, while the peptide exhibited an increased local concentration in the membrane, this did not lead to the induction of membrane permeabilization, as verified by fluorescence methodologies and surface plasmon resonance. These results further support the idea that PrP(106-126) toxicity is not a consequence of peptide-membrane interaction and pore formation.
AB - Prion diseases result from a post-translational modification of the physiological Prion protein (PrPC) into a scrapie isoform (PrPSc). The PrP(106-126) fragment is conserved among various abnormal variants and shows PrPSc pathogenic properties. It has been proposed that the PrP(106-126) fragment may exhibit its toxic effects through membrane channel formation. However our previous studies showed that PrP(106-126) does not interact with membranes under physiological conditions. In the present study, PrP(106-126) affinity for membranes was increased by modifying PrP(106-126) with a M112W substitution and pore formation was further evaluated. However, while the peptide exhibited an increased local concentration in the membrane, this did not lead to the induction of membrane permeabilization, as verified by fluorescence methodologies and surface plasmon resonance. These results further support the idea that PrP(106-126) toxicity is not a consequence of peptide-membrane interaction and pore formation.
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19301918
U2 - 10.1021/bi900009d
DO - 10.1021/bi900009d
M3 - Article
VL - 48
SP - 4198
EP - 4208
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 19
ER -