title: Similarities in the thermodynamics and kinetics of aggregation of disease-related Abeta(1-40) peptides.
abstract: Increasing evidence indicates that polypeptide aggregation often involves a nucleation and a growth phase, although the relationship between the factors that determine these two phases has not yet been fully clarified. We present here an analysis of several mutations at different sites of the Abeta(1-40) peptide, including those associated with early onset forms of the Alzheimer's disease, which reveals that the effects of specific amino acid substitutions in the sequence of this peptide are strongly modulated by their structural context. Nevertheless, mutations at different positions perturb in a correlated manner the free energies of aggregation as well as the lag times and growth rates. We show that these observations can be rationalized in terms of the intrinsic propensities for aggregation of the Abeta(1-40) sequence, thus suggesting that, in the case of this peptide, the determinants of the thermodynamics and of the nucleation and growth of the aggregates have a similar physicochemical basis.
authors.affiliation: Leibniz-Institut für Altersforschung, Fritz-Lipmann-Institut, D-07745 Jena, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Meinhardt
authors.forename: Gian Gaetano
authors.initials: GG
authors.lastname: Tartaglia
authors.forename: Amol
authors.initials: A
authors.lastname: Pawar
authors.forename: Tony
authors.initials: T
authors.lastname: Christopeit
authors.forename: Peter
authors.initials: P
authors.lastname: Hortschansky
authors.forename: Volker
authors.initials: V
authors.lastname: Schroeckh
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
authors.forename: Michele
authors.initials: M
authors.lastname: Vendruscolo
authors.forename: Marcus
authors.initials: M
authors.lastname: Fändrich
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D011489:Protein Denaturation; D017510:Protein Folding; D013816:Thermodynamics
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)