[en] The study of amyloidogenic proteins is of great interest in biochemistry because these proteins undergo a conformational change and an aggregation, that are largely implicated in several incurable diseases including Alzheimer’s, Parkinson’s or Creutzfeldt-Jakob’s disease. In addition, these phenomena are not completely understood, either structurally or energetically. These proteins, in their amyloidogenic conformation, aggregate rapidly in solution and form fibrils that are insoluble and resistant to proteolysis.
Recently, tilted peptides were detected in two of the amyloidogenic proteins involved in neurodegenerative diseases; the amyloid β peptide responsible for Alzheimer’s disease, and the PrP protein that causes Creutzfeldt-Jakob’s disease. Tilted peptides are short protein fragments (11 to 18 residues) that adopt a tilted orientation when inserted into biological membranes, which they are able to destabilise. When helical, tilted peptides present an asymmetric hydrophobicity gradient responsible for their oblique insertion.
Tilted peptides have also been detected in some other amyloidogenic proteins. In a set of 27 amyloidogenic proteins, five tilted peptides from four different proteins have been shown up by molecular modelling. Tilted peptides could be responsible for the neurotoxic effect of these proteins. Thanks to their fusogenic properties, they could interact directly with the membrane leading to cell death. Tilted peptides could also be involved in the tranconformational process of these proteins.
The aim of this study was to characterise experimentally the tilted peptide detected by molecular modelling in the α-synuclein sequence, responsible for Parkinson’s disease. This peptide is tested experimentally to highlight its lipid destabilising properties. Its conformation is studied by IR spectroscopy. The fusogenic assays point to its destabilizing properties.
Research Center/Unit :
Centre de Biophysique Moléculaire Numérique
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Crowet, Jean-Marc ; Université de Liège - ULiège > Chimie et bio-industries > Biophysique moléc. numér.
Language :
French
Title :
Etude expérimentale du peptide oblique de l’α-synucléine
Alternative titles :
[en] Experimental Study of the α-Synuclein Tilted Peptide