Reference : The 118-135 Peptide Lot The Human Prion Protein Forms Amyloid Fibrils And Induces Lip...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
The 118-135 Peptide Lot The Human Prion Protein Forms Amyloid Fibrils And Induces Liposome Fusion
Pillot, T. [> > > >]
Lins, Laurence mailto [Université de Liège - ULiège > > Gembloux Agro-Bio Tech >]
Goethals, M. [> > > >]
Vanloo, B. [> > > >]
Baert, J. [> > > >]
Vandekerckhove, J. [> > > >]
Rosseneu, M. [> > > >]
Brasseur, Robert mailto [Université de Liège - ULiège > > Gembloux Agro-Bio Tech >]
Journal of Molecular Biology
Yes (verified by ORBi)
[en] The prion protein (PrPC) is a glycoprotein of unknown function normally found at
the surface of neurons and of glial cells. It is involved in diseases such as
bovine spongiform encephalopathy, and Creutzfeldt-Jakob disease in the human,
where PrPC is converted into an altered form (termed PrPSc). PrPSc is highly
resistant towards proteolytic degradation and accumulates in the central nervous
system of affected individuals. By analogy with the pathological events occuring
during the development of Alzheimer's disease, controverses still exist regarding
the relationship between amyloidogenesis, prion aggregation and neuronal loss. To
unravel the mechanism of PrP neurotoxicity and understand the interaction of PrP
with cellular membranes, a series of natural and variant peptides spanning
residues 118 to 135 of PrP was synthesized. The potential of these peptides to
induce fusion of unilamellar lipid vesicles was investigated. According to
computer modeling calculations, the 120 to 133 domain of PrP is predicted to be a
tilted lipid-associating peptide, and to insert in a oblique way into a lipid
bilayer through its N-terminal end. In addition to amyloidogenic properties
exhibited in vitro by these peptides, peptide-induced vesicle fusion was
demonstrated by several techniques, including lipid- and core-mixing assays.
Elongation of the 120 to 133 peptide towards the N- and C-terminal ends of the
PrP sequence showed that the 118 to 135 PrP peptide has maximal fusogenic
properties, while the variant peptides had no effect. Due to their high
hydrophobicity, all peptides tested were able to interact with liposomes to
induce leakage of encapsulated calcein. We demonstrate also that the propensity
of the peptides to fold as an alpha-helix increases their fusogenic activity,
thus accounting for the maximal fusogenic activity of the most stable helix at
residues 118 to 135. These data suggest that, by analogy with the C-terminal
domain of the beta-amyloid peptide, the fusogenic properties exhibited by the
prion peptides might contribute to the neurotoxicity of these peptides by
destabilizing cellular membranes.
Researchers ; Professionals

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