期刊
PROTEIN SCIENCE
卷 20, 期 2, 页码 387-395出版社
WILEY
DOI: 10.1002/pro.570
关键词
alpha-synuclein; NMR spectroscopy; structure; amyloid fibril; mutation
资金
- Max Planck Society
- Alexander von Humboldt Foundation
- BMBF [NGFN-Plus 01GS08190]
- European Union [NEURASYNC PITN-GA-2009-238316]
- DFG [ZW 71/2-1, 3-1]
The major component of neural inclusions that are the pathological hallmark of Parkinson's disease are amyloid fibrils of the protein a-synuclein (aS). Here we investigated if the disease-related mutation A30P not only modulates the kinetics of aS aggregation, but also alters the structure of amyloid fibrils. To this end we optimized the method of quenched hydrogen/deuterium exchange coupled to NMR spectroscopy and performed two-dimensional proton-detected high-resolution magic angle spinning experiments. The combined data indicate that the A30P mutation does not cause changes in the number, location and overall arrangement of beta-strands in amyloid fibrils of aS. At the same time, several residues within the fibrillar core retain nano-second dynamics. We conclude that the increased pathogenicity related to the familial A30P mutation is unlikely to be caused by a mutation-induced change in the conformation of aS aggregates.
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