Mapping Long-Range Interactions in α-Synuclein using Spin-Label NMR and Ensemble Molecular Dynamics Simulations
Journal of the American Chemical Society2004Vol. 127(2), pp. 476–477
Citations Over TimeTop 1% of 2004 papers
Matthew M. Dedmon, Kresten Lindorff‐Larsen, John Christodoulou, Michele Vendruscolo, Christopher M. Dobson
Abstract
The intrinsically disordered protein alpha-synuclein plays a key role in the pathogenesis of Parkinson's disease (PD). We show here that the native state of alpha-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 alpha-synuclein aggregates, which are thought to be the cytotoxic species responsible for neurodegeneration in PD.
Related Papers
- → Probing effect of weak H-bonding on conformational change in ionic liquid: Experimental and DFT studies(2018)12 cited
- → Structural information from OH stretching vibrations—XVII. On the different conformers in benzylalcohols and anthracylmethanols(1986)22 cited
- → Relative energies, stereoelectronic interactions and conformational interconversions in silathiacyclohexanes(2004)15 cited
- → Effects of side chains in gas-phase amino acids: Conformational analysis and relative stabilities(2009)7 cited
- → Conformation and vibrational spectra of 1,2-diisocyanoethane(1982)7 cited