論文 - 詳細
| RRC ID | 41487 |
|---|---|
| 著者 | Matsunaga Y, Saito N, Fujii A, Yokotani J, Takakura T, Nishimura T, Esaki H, Yamada T. |
| タイトル | A pH-dependent conformational transition of Abeta peptide and physicochemical properties of the conformers in the glial cell. |
| ジャーナル | Biochem J |
| Abstract |
In the present study we identified the epitopes of antibodies against amyloid beta-(1-42)-peptide (Abeta1-42): 4G8 reacted with peptides corresponding to residues 17-21, 6F/3D reacted with peptides corresponding to residues 9-14, and anti 5-10 reacted with peptides corresponding to residues 5-10. The study also yielded some insight into the Abeta1-42 structures resulting from differences in pH. An ELISA study using monoclonal antibodies showed that pH-dependent conformational changes occur in the 6F/3D and 4G8 epitopes modified at pH 4.6, but not in the sequences recognized by anti 1-7 and anti 5-10. This was unique to Abeta1-40 and Abeta1-42 and did not occur with Abeta1-16 or Abeta17-42. The reactivity profile of 4G8 was not affected by blockage of histidine residues of pH-modified Abeta1-40 and Abeta1-42 with diethyl pyrocarbonate; however, the mutant [Gln(11)]Abeta1-40 abrogated the unique pH-dependence towards 4G8 observed with Abeta1-40. These findings suggest that these epitopes are cryptic at pH 4.6, and that Glu(11) is responsible for the changes. We suggest that the abnormal folding of 6F/3D epitope affected by pH masked the 4G8 epitope. A study of the binding of metal ions to Abeta1-42 suggested that Cu(2+) and Zn(2+) induced a conformational transition around the 6F/3D region at pH 7.4, but did not affect the region when it was modified at pH 4.6. However, Fe(2+) had no effect, irrespective of pH. Abeta modified at pH 4.6 appeared to be relatively resistant to proteinase K compared with Abetas modified at pH 7.4, and the former might be preferentially internalized and accumulated in a human glial cell. Our findings suggest the importance of microenvironmental changes, such as pH, in the early stage of formation of Abeta aggregates in the glial cell. |
| 巻・号 | 361(Pt 3) |
| ページ | 547-56 |
| 公開日 | 2002-2-1 |
| DOI | 10.1042/0264-6021:3610547 |
| PMID | 11802784 |
| PMC | PMC1222337 |
| MeSH | Alzheimer Disease / metabolism Amino Acid Sequence Amino Acids / chemistry Amyloid beta-Peptides / chemistry* Antibodies, Monoclonal / metabolism Blotting, Western Cell Line Densitometry Enzyme-Linked Immunosorbent Assay Epitope Mapping Epitopes Histidine / chemistry Humans Hydrogen-Ion Concentration Iron / chemistry Molecular Sequence Data Neuroglia / cytology* Peptide Biosynthesis Protein Binding Protein Conformation Protein Structure, Tertiary Sequence Homology, Amino Acid Time Factors |
| IF | 4.097 |
| 引用数 | 17 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | KG-1-C(RCB0270) |