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          Institute: MPI für biophysikalische Chemie     Collection: Molekulare Biologie (Dr. Thomas M. Jovin)     Display Documents



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ID: 204773.0, MPI für biophysikalische Chemie / Molekulare Biologie (Dr. Thomas M. Jovin)
Double-stranded DNA stimulates the fibrillation of α-synuclein in vitro and is associated with the mature fibrils: An electron microscopy study
Authors:Cherny, D. I.; Hoyer, W.; Subramaniam, V.; Jovin, T. M.
Language:English
Date of Publication (YYYY-MM-DD):2004-12
Title of Journal:Journal of Molecular Biology
Volume:344
Start Page:929
End Page:938
Sequence Number of Article:doi:10.1016/j.jmb.2004.09.096
Copyright:c* 2004 Elsevier Ltd.
Review Status:not specified
Audience:Not Specified
Abstract / Description:Filamentous aggregates formed by α-synuclein are a prominent and presumably key etiological factor in Parkinson’s and other neurodegenerative diseases characterized by motor disorders. Numerous studies have demonstrated that various environmental and intracellular factors affect the fibrillation properties of α-synuclein, e.g. by accelerating the process of assembly. Histones, the major component and constituent of chromatin, interact specifically with α-synuclein and enhance its fibrillation significantly. Here, we report that another component of chromatin, double-stranded DNA (dsDNA), either linear or supercoiled, also interacts with wild-type α-synuclein, leading to a significant stimulation of α-synuclein assembly into mature fibrils characterized by a reduced lag phase. In general, the morphology of the fibrils remains unchanged in the presence of linear dsDNA. Electron microscopy reveals that DNA forms various types of complexes upon association with the fibrils at their surface without distortion of the double-helical structure. The existence of these complexes was confirmed by the electrophoresis, which also demonstrated that a fraction of the associated DNA was resistant to digestion by restriction endonucleases. Fibrils assembled from the α-synuclein mutants A30P and A53T and the C-terminally truncated variants (encoding amino acid residues 1–108 or 1–124) also form complexes with linear dsDNA. Possible mechanisms and implications of dsDNA–α-synuclein interactions are discussed.
Free Keywords:α-synuclein, amyloid fibril, β-sheet, DNA-fibril interaction, electron microscopy
Last Change of the Resource (YYYY-MM-DD):2004-11-17
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für biophysikalische Chemie/Abt. Thomas Jovin / 060
External Affiliations:Institute of Molecular Genetics, Russian Academy of Sciences, Kurchatov's Square, 123182 Moscow, Russia; Biophysical Engineering Group, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands
Identifiers:URL:http://www.sciencedirect.com/science?_ob=MImg&_ima...
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