Density functional theory analysis and spectral studies on amyloid peptide Abeta(28-35) and its mutants A30G and A30I.
J Struct Biol
; 170(3): 439-50, 2010 Jun.
Article
em En
| MEDLINE
| ID: mdl-20188180
ABSTRACT
Folding and self-assembly of amyloid beta (Abeta) peptide are linked to Alzheimer's disease. To understand the initial stage of amyloid-beta peptide aggregation, conformational characteristics of monomers of wild-type (WT) Abeta(28-35) and its mutant peptides A30G and A30I were investigated using density functional theory calculations and experimental studies. Monomeric structures and their relative stabilities were obtained on the basis of systematic structural optimization in the gas-phase and in the aqueous medium. Computations were performed by hybrid Hartree-Fock-Density Functional Theory (HF-DFT) at B3LYP/6-31G * level. Experimentally, the conformational transitions in the early stages of the octapeptide Abeta(28-35) and its mutants A30G and A30I in solution were characterized by CD, Thioflavin assay and FRET spectroscopy. Examination of the secondary structures revealed that Abeta(28-35) and its mutant monomers exist in random coil conformation in the aqueous medium in agreement with the theoretical predictions, which upon aging is transformed to sheet with different kinetics. This study deals with the structurally important intermediates and it may help to understand the mechanism of amyloid fibril aggregation leading to the onset of Alzheimer's disease.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Peptídeos beta-Amiloides
/
Proteínas Mutantes
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Struct Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Índia