[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/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 :
Détection et caractérisation de peptides obliques au sein de protéines amyloïdogéniques
Alternative titles :
[en] Detection and characterization of tilted peptides in amyloid proteins
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