Doctoral thesis (Dissertations and theses)
Détection et caractérisation de peptides obliques au sein de protéines amyloïdogéniques
Crowet, Jean-Marc
2008
 

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Abstract :
[en] The study of amyloidogenic proteins is of interest in biochemistry because these proteins undergo conformational changes and aggregation. Both processes are largely implicated in several diseases including Alzheimer’s, Parkinson’s or Creutzfeldt-Jakob’s disease. These phenomena are not completely understood, either at a structural or energetical point of view. Tilted peptides are short protein fragment (11 to 19 residues) that adopt a tilted orientation when inserted into biological membranes and destabilise them. Recently, tilted peptides have been detected in two 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 could be responsible for the neurotoxic effects of these proteins. Due to their destabilising properties, they could interact directly with the membrane leading to cell death. Tilted peptides could also be involved in the transconformational process of the proteins. The aim of this work is to detect tilted fragments in other amyloidogenic proteins by molecular modelling and to study some of these peptides experimentally to evidence their lipid destabilizing properties, their structure and their toxicity. In addition, this work enable the design of an automatic method of detection for tilted peptides. Twenty-two tilted peptides from 18 different proteins have been detected among 53 amyloidogenic proteins and 7 peptides were tested experimentally. The results support the hypothesis that some tilted peptides could be involved in transconformational processes and/or cytotoxicity related to amyloidogenic proteins.
Research center :
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 :
Détection et caractérisation de peptides obliques au sein de protéines amyloïdogéniques
Alternative titles :
[en] Detection and characterization of tilted peptides in amyloid proteins
Defense date :
07 May 2008
Number of pages :
217
Institution :
ULiège. GxABT - Liège Université. Gembloux Agro-Bio Tech
Degree :
Docteur en Sciences Agronomiques et Ingénierie Biologique
Promotor :
Brasseur, Robert ;  Université de Liège - ULiège > Département GxABT > Chimie des agro-biosystèmes
Lins, Laurence  ;  Université de Liège - ULiège > Département GxABT > Chimie des agro-biosystèmes
President :
Thewis, André ;  Université de Liège - ULiège > Département GxABT > Ingénierie des productions animales et nutrition
Jury member :
Deleu, Magali  ;  Université de Liège - ULiège > Département GxABT > Chimie des agro-biosystèmes
Nguyen Van-Distèche, Martine ;  Université de Liège - ULiège > Centres généraux > Centre d'ingénierie des protéines
Paquot, Michel ;  Université de Liège - ULiège > Département GxABT > Microbial, food and biobased technologies
Portetelle, Daniel ;  Université de Liège - ULiège > Département GxABT > Microbial, food and biobased technologies
Deroanne, Claude
Dufrene, Yves
Name of the research project :
Etude de l’implication des peptides obliques dans les phénomènes de transconformation
Funders :
FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture [BE]
Available on ORBi :
since 10 December 2013

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