This title appears in the Scientific Report :
2015
Please use the identifier:
http://dx.doi.org/10.1002/anie.201503018 in citations.
Contact between the β1 and β2 Segments of α-Synuclein that Inhibits Amyloid Formation
Contact between the β1 and β2 Segments of α-Synuclein that Inhibits Amyloid Formation
Conversion of the intrinsically disordered protein α-synuclein (α-syn) into amyloid aggregates is a key process in Parkinson’s disease. The sequence region 35–59 contains β-strand segments β1 and β2 of α-syn amyloid fibril models and most disease-related mutations. β1 and β2 frequently engage in tra...
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Personal Name(s): | Shaykhalishahi, Hamed |
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Gauhar, Aziz / Wördehoff, Michael M. / Grüning, Clara S. R. / Klein, Antonia N. / Bannach, Oliver / Stoldt, Matthias / Willbold, Dieter / Härd, Torleif / Hoyer, Wolfgang (Corresponding author) | |
Contributing Institute: |
Strukturbiochemie; ICS-6 |
Published in: | Angewandte Chemie / International edition, 54 (2015) 30, S. 8837 - 8840 |
Imprint: |
Weinheim
Wiley-VCH
2015
|
DOI: |
10.1002/anie.201503018 |
PubMed ID: |
26119103 |
Document Type: |
Journal Article |
Research Program: |
Physical Basis of Diseases |
Publikationsportal JuSER |
Conversion of the intrinsically disordered protein α-synuclein (α-syn) into amyloid aggregates is a key process in Parkinson’s disease. The sequence region 35–59 contains β-strand segments β1 and β2 of α-syn amyloid fibril models and most disease-related mutations. β1 and β2 frequently engage in transient interactions in monomeric α-syn. The consequences of β1–β2 contacts are evaluated by disulfide engineering, biophysical techniques, and cell viability assays. The double-cysteine mutant α-synCC, with a disulfide linking β1 and β2, is aggregation-incompetent and inhibits aggregation and toxicity of wild-type α-syn. We show that α-syn delays the aggregation of amyloid-β peptide and islet amyloid polypeptide involved in Alzheimer’s disease and type 2 diabetes, an effect enhanced in the α-synCC mutant. Tertiary interactions in the β1–β2 region of α-syn interfere with the nucleation of amyloid formation, suggesting promotion of such interactions as a potential therapeutic approach. |