English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Local and global dynamics in intrinsically disordered synuclein.

MPS-Authors
/persons/resource/persons36515

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

/persons/resource/persons14824

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

/persons/resource/persons16093

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

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)

2640234_Suppl.pdf
(Supplementary material), 2MB

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: https://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.