Journal Article

FZJ-2015-07306

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Contact between the β1 and β2 Segments of α-Synuclein that Inhibits Amyloid Formation

Shaykhalishahi, H.FZJ* ; Gauhar, A. ; Wördehoff, M. M. ; Grüning, C. S. R. ; Klein, A. N.FZJ* ; Bannach, O.FZJ* ; Stoldt, M.FZJ* ; Willbold, D.FZJ* ; Härd, T. ; Hoyer, W. (Corresponding author)FZJ*

2015
Wiley-VCH Weinheim

This record in other databases:      

Please use a persistent id in citations: doi:10.1002/anie.201503018

Abstract: 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.

---

Contributing Institute(s):

1. Strukturbiochemie (ICS-6)

Research Program(s):

1. 553 - Physical Basis of Diseases (POF3-553) (POF3-553)

Appears in the scientific report 2015

---

Database coverage:
; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---