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
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