Parkinson's disease is an age-related movement disorder characterized by the presence in the mid-brain of amyloid deposits of the 140-amino-acid protein AS (α-synuclein). AS fibrillation follows a nucleation polymerization pathway involving diverse transient prefibrillar species varying in size and morphology. Similar to other neurodegenerative diseases, cytotoxicity is currently attributed to these prefibrillar species rather than to the insoluble aggregates. Nevertheless, the underlying molecular mechanisms responsible for cytotoxicity remain elusive and structural studies may contribute to the understanding of both the amyloid aggregation mechanism and oligomer-induced toxicity. It is already recognized that soluble oligomeric AS species adopt β-sheet structures that differ from those characterizing the fibrillar structure. In the present study we used ATR (attenuated total reflection)–FTIR (Fourier-transform infrared) spectroscopy, a technique especially sensitive to β-sheet structure, to get a deeper insight into the β-sheet organization within oligomers and fibrils. Careful spectral analysis revealed that AS oligomers adopt an antiparallel β-sheet structure, whereas fibrils adopt a parallel arrangement. The results are discussed in terms of regions of the protein involved in the early β-sheet interactions and the implications of such conformational arrangement for the pathogenicity associated with AS oligomers.
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Research Article|
April 16 2012
Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure
María Soledad Celej;
María Soledad Celej
1
*Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC, UNC-CONICET), Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, X5000HUA Córdoba, Argentina
1To whom correspondence should be addressed (email mcelej@mail.fcq.unc.edu.ar).
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Rabia Sarroukh;
Rabia Sarroukh
†Centre for Structural Biology and Bioinformatics, Laboratory for Structure and Function of Biological Membranes, Université Libre de Bruxelles, CP 206/2, Blvd. du Triomphe, B-1050 Brussels, Belgium
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Erik Goormaghtigh;
Erik Goormaghtigh
†Centre for Structural Biology and Bioinformatics, Laboratory for Structure and Function of Biological Membranes, Université Libre de Bruxelles, CP 206/2, Blvd. du Triomphe, B-1050 Brussels, Belgium
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Gerardo D. Fidelio;
Gerardo D. Fidelio
*Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC, UNC-CONICET), Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, X5000HUA Córdoba, Argentina
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Jean-Marie Ruysschaert;
Jean-Marie Ruysschaert
†Centre for Structural Biology and Bioinformatics, Laboratory for Structure and Function of Biological Membranes, Université Libre de Bruxelles, CP 206/2, Blvd. du Triomphe, B-1050 Brussels, Belgium
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Vincent Raussens
Vincent Raussens
†Centre for Structural Biology and Bioinformatics, Laboratory for Structure and Function of Biological Membranes, Université Libre de Bruxelles, CP 206/2, Blvd. du Triomphe, B-1050 Brussels, Belgium
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Publisher: Portland Press Ltd
Received:
October 28 2011
Revision Received:
January 30 2012
Accepted:
February 08 2012
Accepted Manuscript online:
February 08 2012
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 443 (3): 719–726.
Article history
Received:
October 28 2011
Revision Received:
January 30 2012
Accepted:
February 08 2012
Accepted Manuscript online:
February 08 2012
Citation
María Soledad Celej, Rabia Sarroukh, Erik Goormaghtigh, Gerardo D. Fidelio, Jean-Marie Ruysschaert, Vincent Raussens; Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure. Biochem J 1 May 2012; 443 (3): 719–726. doi: https://doi.org/10.1042/BJ20111924
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