English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Transient secondary and tertiary structure formation kinetics in the intrinsically disordered state of α-Synuclein from atomistic simulations.

MPS-Authors
/persons/resource/persons41413

Graen,  T.
Department of Theoretical and Computational Biophysics, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons15339

Klement,  R.
Department of Theoretical and Computational Biophysics, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons15155

Grubmüller,  H.
Department of Theoretical and Computational Biophysics, MPI for biophysical chemistry, Max Planck Society;

External Ressource
No external resources are shared
Fulltext (public)

2627982.pdf
(Publisher version), 3MB

Supplementary Material (public)

2627982_Suppl.pdf
(Supplementary material), 16MB

Citation

Graen, T., Klement, R., Grupi, A., Haas, E., & Grubmüller, H. (2018). Transient secondary and tertiary structure formation kinetics in the intrinsically disordered state of α-Synuclein from atomistic simulations. ChemPhysChem, 19(19), 2507-2511. doi:10.1002/cphc.201800504.


Cite as: http://hdl.handle.net/21.11116/0000-0001-DB29-B
Abstract
In the absence of a stable fold, transient secondary structure kinetics define the native state of the prototypical and pharmacologically relevant intrinsically disordered protein (IDP) α-Synuclein (aS). Here, we investigate kinetics preventing ordering and possibly pathogenic β-sheet aggregation. Interestingly, transient β-sheets form frequently at sub μs time scales precisely at the positions observed in aS amyloid fibrils. The formation kinetics competes with rapid secondary structure dissociation rates, thus explaining the low secondary structure content. The fast secondary structure dissociation times are very similar to the dynamics of tertiary structure rearrangements. These findings suggest that the fast dissociation kinetics slows down conformational selection processes for aS aggregation, which may be a general mechanism controlling the aggregation kinetics of IDPs.