A New Amyloid-Like β-Aggregate with Amyloid Characteristics, Except Fibril Morphology
Resource
Journal of Molecular Biology 385 (4): 1257-1265
Journal
Journal of Molecular Biology
Pages
1257-1265
Date Issued
2009
Date
2009
Author(s)
Chang, Evan S.-H.
Liao, Tai-Yan
Lim, Tsong-Shin
Fann, Wunshain
Chen, Rita P.-Y.
Abstract
Amyloid plaques, formed from amyloid beta (Abeta) peptides (mainly Abeta40 or Abeta42), are one of the most important pathological characteristics of Alzheimer's disease. Here, a single D-form proline substitution in the 40-amino-acid Abeta40 peptide can totally change the aggregation behavior of this peptide. The residue immediately preceding each glycine in Abeta40 (S8, V24, I32, and V36) was individually replaced by D-form proline ((D)Pro). The resulting (D)P-G sequence (the (D)Pro residue and the following Gly residue) was designed as a "structural clip" to force the formation of a bend in the peptide, as this sequence has been reported to be a strong promoter of beta-hairpin formation. The mutant peptide with Val24-to-(D)Pro substitution, named V24P, formed a new amyloid-like beta-aggregate at high peptide concentration. The aggregate has most of the characteristics of amyloid fibrils, except fibril morphology. Moreover, the mutant peptide V24P, when mixed with Abeta40, can attenuate the cytotoxicity of Abeta40.
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