Mutant and wild type human alpha-synucleins assemble into elongated filaments with distinct morphologies in vitro

alpha-Synuclein is a soluble presynaptic protein which is pathologically redistributed within intracellular lesions characteristic of several neurodegenerative diseases. Here we demonstrate that wild type and two mutant forms of alpha-synuclein linked to familial Parkinson's disease (Ala30 --&g...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-03, Vol.274 (12), p.7619-7622
Main Authors: Giasson, B I, Uryu, K, Trojanowski, J Q, Lee, V M
Format: Article
Language:English
Subjects:
alpha-Synuclein
Amino Acid Substitution
Cytoskeleton - ultrastructure
Detergents
Humans
Microscopy, Electron
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Parkinson Disease - genetics
Phosphoproteins - genetics
Phosphoproteins - metabolism
Protein Conformation
Sodium Dodecyl Sulfate
Solubility
Synucleins
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Summary:alpha-Synuclein is a soluble presynaptic protein which is pathologically redistributed within intracellular lesions characteristic of several neurodegenerative diseases. Here we demonstrate that wild type and two mutant forms of alpha-synuclein linked to familial Parkinson's disease (Ala30 --> Pro and Ala53 --> Thr) self-aggregate and assemble into 10-19-nm-wide filaments with distinct morphologies under defined in vitro conditions. Immunogold labeling demonstrates that the central region of all these filaments are more robustly labeled than the N-terminal or C-terminal regions, suggesting that the latter regions are buried within the filaments. Since in vitro generated alpha-synuclein filaments resemble the major ultrastructural elements of authentic Lewy bodies that are hallmark lesions of Parkinson's disease, we propose that self-aggregating alpha-synuclein is the major subunit protein of these filamentous lesions.
ISSN:0021-9258
DOI:10.1074/jbc.274.12.7619