TY  - JOUR
AU  - Shaykhalishahi, Hamed
AU  - Gauhar, Aziz
AU  - Wördehoff, Michael M.
AU  - Grüning, Clara S. R.
AU  - Klein, Antonia N.
AU  - Bannach, Oliver
AU  - Stoldt, Matthias
AU  - Willbold, Dieter
AU  - Härd, Torleif
AU  - Hoyer, Wolfgang
TI  - Contact between the β1 and β2 Segments of α-Synuclein that Inhibits Amyloid Formation
JO  - Angewandte Chemie / International edition
VL  - 54
IS  - 30
SN  - 1433-7851
CY  - Weinheim
PB  - Wiley-VCH
M1  - FZJ-2015-07306
SP  - 8837 - 8840
PY  - 2015
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000358051600050
C6  - pmid:26119103
DO  - DOI:10.1002/anie.201503018
UR  - https://juser.fz-juelich.de/record/279291
ER  -