Alteration of the α-Synuclein Folding Landscape by a Mutation Related to Parkinson's Disease

Shape shifting linked to disease: A single‐molecule fluorescence technique was used to probe structures of an intrinsically disordered brain protein. A mutation was found to tilt the coupled binding–folding energy landscape of the protein and inhibited switching between induced ordered structures (s...

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Published inAngewandte Chemie (International ed.) Vol. 49; no. 20; pp. 3469 - 3472
Main Authors Ferreon, Allan Chris M, Moran, Crystal R, Ferreon, Josephine C, Deniz, Ashok A
Format Journal Article
LanguageEnglish
Published Weinheim Wiley-VCH Verlag 03.05.2010
WILEY-VCH Verlag
WILEY‐VCH Verlag
Subjects
alpha-Synuclein - chemistry
alpha-Synuclein - genetics
alpha-Synuclein - metabolism
Circular Dichroism
Communication
conformational switching
FRET
Models, Molecular
Mutation
Parkinson Disease - genetics
Parkinson Disease - metabolism
Protein Folding
Protein Structure, Secondary
single-molecule biophysics
Thermodynamics
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Summary:Shape shifting linked to disease: A single‐molecule fluorescence technique was used to probe structures of an intrinsically disordered brain protein. A mutation was found to tilt the coupled binding–folding energy landscape of the protein and inhibited switching between induced ordered structures (see picture). The observations provide fundamental insight into the molecular basis of Parkinson's disease.
Bibliography:http://dx.doi.org/10.1002/anie.201000378
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We thank Dr. Yann Gambin, and Dr. Jeffrey W. Kelly and co-workers for technical assistance, and Dr. Peter E. Wright for use of the CD spectrometer. The wild-type α-synuclein plasmid construct was a generous gift from Dr. Robert L. Nussbaum (National Institutes of Health, Bethesda). This research was supported by grant RO1 GM066833 from the National Institute of General Medical Sciences, NIH to A.A.D., and postdoctoral fellowships from the National Institute of Neurological Disorders and Stroke, NIH (A.C.M.F.) and the Leukemia and Lymphoma Society (J.C.F.).
NIH
ArticleID:ANIE201000378
These authors contributed equally.
We thank Dr. Yann Gambin, and Dr. Jeffrey W. Kelly and co‐workers for technical assistance, and Dr. Peter E. Wright for use of the CD spectrometer. The wild‐type α‐synuclein plasmid construct was a generous gift from Dr. Robert L. Nussbaum (National Institutes of Health, Bethesda). This research was supported by grant RO1 GM066833 from the National Institute of General Medical Sciences, NIH to A.A.D., and postdoctoral fellowships from the National Institute of Neurological Disorders and Stroke, NIH (A.C.M.F.) and the Leukemia and Lymphoma Society (J.C.F.).
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We thank Dr. Yann Gambin, and Dr. Jeffrey W. Kelly and co-workers for technical assistance, and Dr. Peter E. Wright for use of the CD spectrometer. The wild-type α-synuclein plasmid construct was a generous gift from Dr. Robert L. Nussbaum (National Institutes of Health, Bethesda). This research was supported by grant RO1 GM066833 from the National Institute of General Medical Sciences, NIH to A.A.D., and postdoctoral fellowships from the National Institute of Neurological Disorders and Stroke, NIH (A.C.M.F.) and the Leukemia and Lymphoma Society (J.C.F.).
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201000378