Reference : In Silico tilted properties of the 67-78 fragment of alpha-synuclein are responsible for...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/23340
In Silico tilted properties of the 67-78 fragment of alpha-synuclein are responsible for membrane destabilization and neurotoxicity
English
Crowet, Jean-Marc [> > > >]
Lins, Laurence mailto [Université de Liège - ULg > Chimie et bio-industries > Biophysique moléc. numér. >]
Dupiereux-Fettweis, Ingrid mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Histologie humaine >]
Elmoualij, Benaïssa mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Histologie humaine >]
Lorin, Aurélien [> > > >]
Charloteaux, Benoît [Université de Liège - ULg > > Gembloux Agro-Bio Tech >]
Stroobant, Vincent [> > > >]
Heinen, Ernst mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Histologie humaine >]
Brasseur, Robert mailto [Université de Liège - ULg > > Gembloux Agro-Bio Tech >]
Sep-2007
Proteins-Structure Function and Bioinformatics
Wiley Liss, Inc.
68
4
936-947
Yes (verified by ORBi)
International
0887-3585
1097-0134
Hoboken
NY
[en] Circular Dichroism ; hydrophobicity ; lipid-interacting peptides ; molecular modelling ; Neurotoxins/toxicity ; Parkinson ; Peptide Fragments/toxicity ; Phospholipids ; Stress, Mechanical ; tilted peptides
[en] Alpha-synuclein is a 140 residue protein associated with Parkinson's disease. Intraneural inclusions called Lewy bodies and Lewy neurites are mainly composed of alpha-synuclein aggregated into amyloid fibrils. Other amyloidogenic proteins, such as the beta amyloid peptide involved in Alzheimer's disease and the prion protein (PrP) associated with Creuztfeldt-Jakob's disease, are known to possess "tilted peptides". These peptides are short protein fragments that adopt an oblique orientation at a hydrophobic/hydrophilic interface, which enables destabilization of the membranes. In this paper, sequence analysis and molecular modelling predict that the 67-78 fragment of alpha-synuclein is a tilted peptide. Its destabilizing properties were tested experimentally. The alpha-synuclein 67-78 peptide is able to induce lipid mixing and leakage of unilamellar liposomes. The neuronal toxicity, studied using human neuroblastoma cells, demonstrated that the alpha-synuclein 67-78 peptide induces neurotoxicity. A mutant designed by molecular modelling to be amphipathic was shown to be significantly less fusogenic and toxic than the wild type. In conclusion, we have identified a tilted peptide in alpha-synuclein, which could be involved in the toxicity induced during amyloidogenesis of alpha-synuclein.
Researchers ; Professionals
http://hdl.handle.net/2268/23340
also: http://hdl.handle.net/2268/63345
10.1002/prot.21483
* Crowet Jean-Marc et Lins Laurence 1er co-auteurs

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