| RRC ID |
73009
|
| 著者 |
Morimoto A, Irie K, Murakami K, Ohigashi H, Shindo M, Nagao M, Shimizu T, Shirasawa T.
|
| タイトル |
Aggregation and neurotoxicity of mutant amyloid beta (A beta) peptides with proline replacement: importance of turn formation at positions 22 and 23.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
Aggregation of the amyloid beta peptides (A beta 1-42 and A beta 1-40) plays a pivotal role in pathogenesis of Alzheimer's disease. Although it is widely accepted that the aggregates of A betas mainly consist of beta-sheet structure, the precise aggregation mechanism remains unclear. To identify amino acid residues that are important for the beta-sheet formation, a series of proline-substituted mutants of A beta 1-42 peptides at positions 19-26 was synthesized in a highly pure form and their aggregation ability and neurotoxicity on PC12 cells were investigated. All proline-substituted A beta 1-42 mutants except for 22P- and 23P-A beta 1-42 were hard to aggregate and showed weaker cytotoxicity than wild-type A beta 1-42, suggesting that the residues at positions 19-21 and 24-26 are important for the beta-sheet formation. In contrast, 22P-A beta 1-42 extensively aggregated with stronger cytotoxicity than wild-type A beta 1-42. Since proline has a propensity for beta-turn structure as a Pro-X corner, these data implicate that beta-turn formation at positions 22 and 23 plays a crucial role in the aggregation and neurotoxicity of A beta peptides.
|
| 巻・号 |
295(2)
|
| ページ |
306-11
|
| 公開日 |
2002-7-12
|
| DOI |
10.1016/s0006-291x(02)00670-8
|
| PII |
S0006291X02006708
|
| PMID |
12150948
|
| MeSH |
Amino Acid Sequence
Amyloid beta-Peptides / chemistry
Amyloid beta-Peptides / metabolism
Amyloid beta-Peptides / physiology*
Animals
Chromatography, High Pressure Liquid
Molecular Sequence Data
PC12 Cells
Peptide Fragments / chemistry
Peptide Fragments / metabolism
Peptide Fragments / physiology*
Proline / chemistry*
Protein Structure, Secondary
Rats
Sequence Homology, Amino Acid
|
| IF |
2.985
|
| リソース情報 |
| ヒト・動物細胞 |
PC-12(RCB0009) |
