Water Distribution, Dynamics and Interactions with Alzheimer's ?-Amyloid Fibrils Investigated by Solid-State NMR.
Water Distribution, Dynamics and Interactions with Alzheimer's ?-Amyloid Fibrils Investigated by Solid-State NMR.
J Am Chem Soc. 2017 Apr 13;:
Authors: Wang T, Jo H, DeGrado WF, Hong M
Abstract
Water is essential for protein folding and assembly of amyloid fibrils. Internal water cavities have been proposed for several amyloid fibrils, but no direct structural and dynamical data have been reported on the water dynamics and site-specific interactions of water with the fibrils. Here we use solid-state NMR spectroscopy to investigate the water interactions of several A?40 fibrils. 1H spectral lineshapes, T2 relaxation times, and 2D 1H-13C correlation spectra show that there are five distinct water pools: three are peptide-bound water while two are highly dynamic water that can be assigned to interfibrillar water and bulk-like matrix water. All these water pools are associated with the fibrils on the nanometer scale. Water-transferred 2D correlation spectra allow us to map out residue-specific hydration, and give evidence for the presence of a water pore in the center of the three-fold symmetric wild-type A?40 fibril. In comparison, the loop residues and the intramolecular strand-strand interface have low hydration, excluding the presence of significant water cavities in these regions. The Osaka A?40 mutant shows lower hydration and more immobilized water than wild-type A?40, indicating the influence of peptide structure on the dynamics and distribution of hydration water. Finally, the highly mobile interfibrillar and matrix water exchange with each other on the timescale of seconds, suggesting that fibril bundling separates these two water pools, and water molecules must diffuse along the fibril axis before exchanging between these two environments. These results provide insights and experimental constraints on the spatial distribution and dynamics of water pools in these amyloid fibrils.
PMID: 28406028 [PubMed - as supplied by publisher]
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