Title: Energy barriers for HET-s prion forming domain amyloid formation
Authors: Sabaté, R
Castillo Cano, Virginia
Espargaró, A
Saupe, Sven J
Ventura, S # ×
Issue Date: Sep-2009
Publisher: Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies
Series Title: FEBS Journal vol:276 issue:18 pages:5053-64
Article number: 10.1111/j.1742-4658.2009.07202.x
Abstract: The prion-forming domain comprising residues 218-289 of the fungal prion HET-s forms infectious amyloid fibrils at physiological pH. Because a high-resolution molecular model for the structure of these fibrils exists, it constitutes an attractive system with which to study the mechanism of amyloid assembly. Understanding aggregation under specific conditions requires a quantitative knowledge of the kinetics and thermodynamics of the self-assembly process. We report here the study of the temperature and agitation dependence of the HET-s(218-289) fibril nucleation (kn) and elongation (ke) rate constants at physiological pH. Over our temperature and agitation range, kn and ke increased 30-fold and three-fold, respectively. Both processes followed the Arrhenius law, allowing calculation of the thermodynamic activation parameters associated with them. The data confirm the nucleation reaction as the rate-limiting step of amyloid fibril formation. The formation of the nucleus appears to depend mainly on enthalpic factors, whereas both enthalpic and entropic effects contribute similarly to the energy barrier to fibril elongation. A kinetic model is proposed in which nucleation depends on the presence of an initially collapsed, but poorly structured, HET-s(218-289) state and in which the fibril tip models the conformation of the incoming monomers without substantial disorganization of its structure during the elongation process.
ISSN: 1742-464X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science