Stability of Osaka Mutant and Wild-Type Fibril Models
| Autor: | Erik J. Alred, Workalemahu M. Berhanu, Ulrich H. E. Hansmann |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Mutation Amyloid beta-Peptides Chemistry Water flow Mutant Wild type Aggregation rate Hydrogen Bonding macromolecular substances Fibril medicine.disease_cause Protein Structure Secondary Surfaces Coatings and Films Protein structure Water channel Biochemistry Materials Chemistry Biophysics medicine Physical and Theoretical Chemistry |
| Zdroj: | The Journal of Physical Chemistry B. 119:13063-13070 |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/acs.jpcb.5b07987 |
| Popis: | Single amino acid mutations in amyloid-beta (Aβ) peptides can lead to early onset and increased severity of Alzheimer's disease. An example is the Osaka mutation (Aβ1-40E22D), which is more toxic than wild-type Aβ1-40. This mutant quickly forms early stage fibrils, one of the hallmarks of the disease, and these fibrils can even seed fibrilization of wild-type monomers. Using molecular dynamic simulations, we show that because of formation of various intra- and intermolecular salt bridges the Osaka mutant fibrils are more stable than wild-type fibrils. The mutant fibril also has a wider water channel with increased water flow than the wild type. These two observations can explain the higher toxicity and aggregation rate of the Osaka mutant over the wild type. |
| Databáze: | OpenAIRE |
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