Mapping Long-Range Interactions in a-Synuclein using Spin-Label NMR and Ensemble Molecular Dynamics Simulations

TY - JOUR

T1 - Mapping Long-Range Interactions in a-Synuclein using Spin-Label NMR and Ensemble Molecular Dynamics Simulations

AU - Dedmon, M. M.

AU - Lindorff-Larsen, K.

AU - Christodoulou, J.

AU - Vendruscolo, Michele

AU - Dobson, C. M.

PY - 2005

Y1 - 2005

N2 - The intrinsically disordered protein a-synuclein plays a key role in the pathogenesis of Parkinson's disease (PD). We show here that the native state of a-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 a-synuclein aggregates, which are thought to be the cytotoxic species responsible for neurodegeneration in PD.

AB - The intrinsically disordered protein a-synuclein plays a key role in the pathogenesis of Parkinson's disease (PD). We show here that the native state of a-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 a-synuclein aggregates, which are thought to be the cytotoxic species responsible for neurodegeneration in PD.

U2 - 10.1021/ja044834j

DO - 10.1021/ja044834j

M3 - Journal article

C2 - 15643843

SN - 0002-7863

VL - 127

SP - 476

EP - 477

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 2

ER -