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Stability of Osaka Mutant and Wild-Type Fibril Models
- Source :
- The Journal of Physical Chemistry B. 119:13063-13070
- Publication Year :
- 2015
- Publisher :
- American Chemical Society (ACS), 2015.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15205207 and 15206106
- Volume :
- 119
- Database :
- OpenAIRE
- Journal :
- The Journal of Physical Chemistry B
- Accession number :
- edsair.doi.dedup.....cadd4777b9f67f5d4d679a2465197cf1