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Journal Article

Reorientational dynamics of amyloid-β from NMR spin relaxation and molecular simulation.

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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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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., & Zweckstetter, M. (2019). Reorientational dynamics of amyloid-β from NMR spin relaxation and molecular simulation. Journal of Physical Chemistry Letters, 10, 3369-3375. doi:10.1021/acs.jpclett.9b01050.


Cite as: http://hdl.handle.net/21.11116/0000-0003-CB85-2
Abstract
Amyloid-β (Aβ) aggregation is a hallmark of Alzheimer's disease. As an intrinsically disordered protein, Aβ undergoes extensive dynamics on multiple length and time scales. Access to a comprehensive picture of the reorientational dynamics in Aβ requires therefore the combination of complementary techniques. Here, we integrate 15N spin relaxation rates at three magnetic fields with microseconds-long molecular dynamics simulation, ensemble-based hydrodynamic calculations, and previously published nanosecond fluorescence correlation spectroscopy to investigate the reorientational dynamics of Aβ1-40 (Aβ40) at single-residue resolution. The integrative analysis shows that librational and dihedral angle fluctuations occurring at fast and intermediate time scales are not sufficient to decorrelate orientational memory in Aβ40. Instead, slow segmental motions occurring at ∼5 ns are detected throughout the Aβ40 sequence and reach up to ∼10 ns for selected residues. We propose that the modulation of time scales of reorientational dynamics with respect to intra- and intermolecular diffusion plays an important role in disease-related Aβ aggregation.