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Structural transformation and aggregation of human alpha-synuclein in trifluoroethanol: non-amyloid component sequence is essential and beta-sheet formation is prerequisite to aggregation.
- Source :
-
Biopolymers [Biopolymers] 2002 Aug 05; Vol. 64 (4), pp. 221-6. - Publication Year :
- 2002
-
Abstract
- Amyloid-like aggregation of alpha-synuclein and deposit in Lewy bodies are thought to be the major cause of Parkinson's disease. Here we describe the secondary structural transformation and aggregation of human alpha-synuclein and its C-terminus truncated fragments in trifluoroethanol. Proteins containing the NAC (non-amyloid component) segment undergo a three-state transition: from native random coil to beta-sheet and to alpha-helical structure, while the NAC deficient fragment and gamma-synuclein undergo a typical two-state coil-to-alpha transition. The beta-sheet form is highly hydrophobic that strongly binds to 1-anilinonaphthalene-8-sulfonic acid (ANS) and is prone to self-aggregation. The results suggest that the NAC sequence is essential to beta-sheet formation and the aggregation originates from the beta-sheet intermediate, which may be implicated in the pathogenesis of Parkinson's disease.<br /> (Copyright 2002 Wiley Periodicals, Inc. Biopolymers 64: 221-226, 2002)
- Subjects :
- Biopolymers chemistry
Circular Dichroism
Humans
In Vitro Techniques
Macromolecular Substances
Parkinson Disease etiology
Peptide Fragments chemistry
Protein Structure, Secondary
Spectrometry, Fluorescence
Synucleins
Trifluoroethanol
alpha-Synuclein
gamma-Synuclein
Nerve Tissue Proteins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3525
- Volume :
- 64
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biopolymers
- Publication Type :
- Academic Journal
- Accession number :
- 12115139
- Full Text :
- https://doi.org/10.1002/bip.10179