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Proc Natl Acad Sci U S A. 2015 May 19;112(20):6365-70. doi: 10.1073/pnas.1422824112. Epub 2015 Apr 27.

Hydration water mobility is enhanced around tau amyloid fibers.

Author information

1
Université Grenoble Alpes, CNRS, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Structurale, 38044 Grenoble, France; martin.weik@ibs.fr yann.fichou@ibs.fr dtobias@uci.edu.
2
Université Grenoble Alpes, CNRS, and Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut de Biologie Structurale, 38044 Grenoble, France;
3
Life Sciences Group, Institut Laue-Langevin, 38000 Grenoble, France;
4
Institut Laue Langevin, 38000 Grenoble, France; Institut Charles Sadron CNRS-UdS, 67034 Strasbourg, France;
5
Jülich Centre for Neutron Science, outstation at Heinz Maier-Leibnitz Zentrum, Forschungszentrum Jülich GmbH, 85747 Garching, Germany;
6
CNRS, UMR 5628, LMGP, 38016 Grenoble, France; Université de Grenoble Alpes, Grenoble Institute of Technology, 38016 Grenoble, France;
7
Life Sciences Group, Institut Laue-Langevin, 38000 Grenoble, France; Faculty of Natural Sciences, Keele University, Staffordshire ST5 5BG, United Kingdom; and.
8
Department of Chemistry, University of California, Irvine, CA 92697-2025 martin.weik@ibs.fr yann.fichou@ibs.fr dtobias@uci.edu.

Abstract

The paired helical filaments (PHF) formed by the intrinsically disordered human protein tau are one of the pathological hallmarks of Alzheimer disease. PHF are fibers of amyloid nature that are composed of a rigid core and an unstructured fuzzy coat. The mechanisms of fiber formation, in particular the role that hydration water might play, remain poorly understood. We combined protein deuteration, neutron scattering, and all-atom molecular dynamics simulations to study the dynamics of hydration water at the surface of fibers formed by the full-length human protein htau40. In comparison with monomeric tau, hydration water on the surface of tau fibers is more mobile, as evidenced by an increased fraction of translationally diffusing water molecules, a higher diffusion coefficient, and increased mean-squared displacements in neutron scattering experiments. Fibers formed by the hexapeptide (306)VQIVYK(311) were taken as a model for the tau fiber core and studied by molecular dynamics simulations, revealing that hydration water dynamics around the core domain is significantly reduced after fiber formation. Thus, an increase in water dynamics around the fuzzy coat is proposed to be at the origin of the experimentally observed increase in hydration water dynamics around the entire tau fiber. The observed increase in hydration water dynamics is suggested to promote fiber formation through entropic effects. Detection of the enhanced hydration water mobility around tau fibers is conjectured to potentially contribute to the early diagnosis of Alzheimer patients by diffusion MRI.

KEYWORDS:

amyloid fibers; hydration water; intrinsically disordered proteins; neutron scattering; tau protein

PMID:
25918405
PMCID:
PMC4443308
DOI:
10.1073/pnas.1422824112
[Indexed for MEDLINE]
Free PMC Article

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