| Autor: |
Na, Sun, Rudolf, Hartmann, Justin, Lecher, Matthias, Stoldt, Susanne Aileen, Funke, Lothar, Gremer, Hans-Henning, Ludwig, Hans-Ulrich, Demuth, Martin, Kleinschmidt, Dieter, Willbold |
| Rok vydání: |
2012 |
| Předmět: |
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| Zdroj: |
Journal of peptide science : an official publication of the European Peptide Society. 18(11) |
| ISSN: |
1099-1387 |
| Popis: |
The aggregation of the Aβ plays a fundamental role in the pathology of AD. Recently, N-terminally modified Aβ species, pE-Aβ, have been described as major constituents of Aβ deposits in the brains of AD patients. pE-Aβ has an increased aggregation propensity and shows increased toxicity compared with Aβ1-40 and Aβ1-42. In the present work, high-resolution NMR spectroscopy was performed to study pE-Aβ3-40 in aqueous TFE-containing solution. Two-dimensional TOCSY and NOESY experiments were performed. On the basis of NOE and chemical shift data, pE-Aβ3-40 was shown to contain two helical regions formed by residues 14-22 and 30-36. This is similar as previously described for Aβ1-40. However, the secondary chemical shift data indicate decreased helical propensity in pE-Aβ3-40 when compared with Aβ1-40 under exactly the same conditions. This is in agreement with the observation that pE-Aβ3-40 shows a drastically increased tendency to form β-sheet-rich structures under more physiologic conditions. Structural studies of pE-Aβ are crucial for better understanding the structural basis of amyloid fibril formation in the brain during development of AD, especially because an increasing number of reports indicate a decisive role of pE-Aβ for the pathogenesis of AD. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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