| RRC ID |
18611
|
| 著者 |
Sohma Y, Wang H, Taniguchi A, Hirayama Y, Kakizawa T, Yamasaki M, Mukai H, Kiso Y.
|
| タイトル |
Self-assembly pathways of E22Δ-type amyloid β peptide mutants generated from non-aggregative O-acyl isopeptide precursors.
|
| ジャーナル |
Bioorg Med Chem
|
| Abstract |
The recently identified E22Δ-type amyloid β peptide (Aβ) mutants are reported to favor oligomerization over fibrillization and to exhibit more-potent synaptotoxicity than does wild-type (WT) Aβ. Aβ(E22Δ) mutants can thus be expected to serve as tools for clarifying the impact of Aβ oligomers in Alzheimer's disease (or Alzheimer's-type dementia). However, the biochemical and biophysical properties of Aβ(E22Δ) have not been conclusively determined. Here, we evaluated the self-assembly pathways of Aβ(E22Δ) mutants generated from water-soluble, non-aggregative O-acyl isopeptide precursors. Circular dichroism spectroscopy, Western blot analysis, and thioflavin-T fluorescence intensity and cellular toxicity assays suggest that the self-assembly pathways of Aβ(E22Δ) differed from those of Aβ(WT). Aβ1-40(E22Δ) underwent a rapid random coil→β-sheet conformational change in its monomeric or low-molecular-weight oligomeric states, whereas Aβ1-40(WT) self-assembled gradually without losing its propensity to form random coil structures. The Aβ1-42(E22Δ) monomer formed β-sheet-rich oligomers more rapidly than did Aβ1-42(WT). Additionally, the Aβ1-42(E22Δ) oligomers appear to differ from Aβ1-42(WT) oligomers in size, shape, or both. These results should provide new insights into the functions of Aβ(E22Δ) mutants.
|
| 巻・号 |
19(12)
|
| ページ |
3787-92
|
| 公開日 |
2011-6-15
|
| DOI |
10.1016/j.bmc.2011.04.056
|
| PII |
S0968-0896(11)00345-2
|
| PMID |
21612934
|
| MeSH |
Acylation
Amino Acid Sequence
Amyloid beta-Peptides / genetics
Amyloid beta-Peptides / metabolism*
Animals
Blotting, Western
Cell Survival / drug effects
Circular Dichroism
Click Chemistry
Molecular Sequence Data
Mutation
PC12 Cells
Peptide Fragments / chemistry*
Protein Structure, Secondary
Rats
Signal Transduction
|
| IF |
3.073
|
| 引用数 |
7
|
|
WOS 分野
|
CHEMISTRY, MEDICINAL
CHEMISTRY, ORGANIC
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
PC-12(RCB0009) |
