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Journal Article

Local and global dynamics in intrinsically disordered synuclein.

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Rezaei-Ghaleh,  N.
Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

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Becker,  S.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

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Zweckstetter,  M.
Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

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Citation

Rezaei-Ghaleh, N., Parigi, G., Soranno, A., Holla, A., Becker, S., Schuler, B., et al. (2018). Local and global dynamics in intrinsically disordered synuclein. Angewandte Chemie International Edition, 57(46), 15262-15266. doi:10.1002/anie.201808172.


Cite as: http://hdl.handle.net/21.11116/0000-0002-0CEE-6
Abstract
Intrinsically disordered proteins experience a diverse spectrum of motions that are difficult to characterize with a single experimental technique. Here we combine high- and low-field nuclear spin relaxation, nanosecond fluorescence correlation spectroscopy (nsFCS) and long molecular dynamics simulations of alpha-synuclein, a paradigmatic IDP involved in Parkinson disease, to obtain a comprehensive picture of its conformational dynamics. The combined analysis shows that fast motions below 2 ns caused by local dihedral angle fluctuations and conformational sampling within and between Ramachandran substates decorrelate most of the backbone N-H orientational memory. However, slow motions with correlation times of up to ~13 ns from segmental dynamics are present throughout the alpha-synuclein chain, in particular in its C-terminal domain, and global chain reconfiguration occurs on a timescale of ~ 60 ns. Our study demonstrates that the combination of high- and low-field nuclear spin relaxation together with nsFCS and molecular dynamics simulations is a powerful strategy to determine residue-specific protein dynamics in IDPs at different time and length scales.