| Autor: |
Baumketner, A, Bernstein, SL, Wyttenbach, T, Bitan, G, Teplow, DB, Bowers, MT, Shea, JE |
| Jazyk: |
angličtina |
| Rok vydání: |
2006 |
| Zdroj: |
Baumketner, A; Bernstein, SL; Wyttenbach, T; Bitan, G; Teplow, DB; Bowers, MT; et al.(2006). Amyloid β-protein monomer structure: A computational and experimental study. Protein Science, 15(3), 420-428. doi: 10.1110/ps.051762406. UCLA: Retrieved from: http://www.escholarship.org/uc/item/5kr1c4vg |
| DOI: |
10.1110/ps.051762406. |
| Popis: |
The structural properties of the Aβ42 peptide, a main constituent of the amyloid plaques formed in Alzheimer's disease, were investigated through a combination of ion-mobility mass spectrometry and theoretical modeling. Replica exchange molecular dynamics simulations using a fully atomic description of the peptide and implicit water solvent were performed on the -3 charge state of the peptide, its preferred state under experimental conditions. Equilibrated structures at 300 K were clustered into three distinct families with similar structural features within a family and with significant root mean square deviations between families. An analysis of secondary structure indicates the Aβ42 peptide conformations are dominated by loops and turns but show some helical structure in the C-terminal hydrophobic tail. A second calculation on Aβ42 in a solvent-free environment yields compact structures turned "inside out" from the solution structures (hydrophobic parts on the outside, polar parts on the inside). Ion mobility experiments on the Aβ42 -3 charge state electrosprayed from solution yield a bimodal arrival time distribution. This distribution can be quantitatively fit using cross-sections from dehydrated forms of the three families of calculated solution structures and the calculated solvent-free family of structures. Implications of the calculations on the early stages of aggregation of Aβ42 are discussed. Published by Cold Spring Harbor Laboratory Press. Copyright © 2006 The Protein Society. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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