Mapping Long-Range Interactions in α-Synuclein using Spin-Label NMR and Ensemble Molecular Dynamics Simulations
Top Cited Papers
- 21 December 2004
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 127 (2), 476-477
- https://doi.org/10.1021/ja044834j
Abstract
The intrinsically disordered protein α-synuclein plays a key role in the pathogenesis of Parkinson's disease (PD). We show here that the native state of α-synuclein consists of a broad distribution of conformers with an ensemble-averaged hydrodynamic radius significantly smaller than that expected for a random coil structure. This partial condensation is driven by interactions between the highly charged C-terminus and a large hydrophobic central region of the protein sequence. We suggest that this structure could inhibit the formation of α-synuclein aggregates, which are thought to be the cytotoxic species responsible for neurodegeneration in PD.Keywords
This publication has 17 references indexed in Scilit:
- Determination of an Ensemble of Structures Representing the Denatured State of the Bovine Acyl-Coenzyme A Binding ProteinJournal of the American Chemical Society, 2004
- The idiotypic network in autoimmunity: antibodies that bind antibodies that bind antibodiesNature Medicine, 2004
- Protein folding and misfoldingNature, 2003
- A Protein-Chameleon: Conformational Plasticity of α-Synuclein, a Disordered Protein Involved in Neurodegenerative DisordersJournal of Biomolecular Structure and Dynamics, 2003
- Structural Organization of α-Synuclein Fibrils Studied by Site-directed Spin LabelingOnline Journal of Public Health Informatics, 2003
- Cellular Polyamines Promote the Aggregation of α-SynucleinOnline Journal of Public Health Informatics, 2003
- Long-Range Interactions Within a Nonnative ProteinScience, 2002
- Solvent‐induced collapse of α‐synuclein and acid‐denatured cytochrome cProtein Science, 2001
- Persistence of Native-Like Topology in a Denatured Protein in 8 M UreaScience, 2001
- Synthetic filaments assembled from C‐terminally truncated α‐synucleinFEBS Letters, 1998