Anomalously Rapid Hydration Water Diffusion Dynamics Near DNA Surfaces

Franck, John M.; Ding, Yuan Chun; Stone, Katherine M.; Qin, Peter Z.; Han, Songi

doi:10.1021/jacs.5b05813

Cited by 65 publications

(100 citation statements)

References 77 publications

(195 reference statements)

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“…16–18 ODNP measures the dipolar coupling factor (ξ) between the unpaired electron spin located near the biomolecular surface and the proton spin of the surrounding solvent water. The dipolar coupling factor is dependent on the correlation time (τ) of inter-spin motion between the electron and nuclear spin.…”

Section: Methodsmentioning

confidence: 99%

Hydration Dynamics of a Peripheral Membrane Protein

et al. 2016

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Water dynamics in the hydration shell of the peripheral membrane protein annexin B12 were studied using MD simulations and Overhauser DNP-enhanced NMR. We show that retardation of water motions near phospholipid bilayers is extended by the presence of a membrane-bound protein, up to around 10 Å above that protein. Near the membrane surface, electrostatic interactions with the lipid head groups strongly slow down water dynamics, whereas protein-induced water retardation is weaker and dominates only at distances beyond 10 Å from the membrane surface. The results can be understood from a simple model based on additive contributions from the membrane and the protein to the activation free energy barriers of water diffusion next to the biomolecular surfaces. Furthermore, analysis of the intermolecular vibrations of the water network reveals that retarded water motions near the membrane shift the vibrational modes to higher frequencies, which we used to identify an entropy gradient from the membrane surface towards the bulk water. Our results have implications for processes that take place at lipid membrane surfaces, including molecular recognition, binding, and protein-protein interactions.

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Section: Methodsmentioning

confidence: 99%

Hydration Dynamics of a Peripheral Membrane Protein

et al. 2016

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“…Thus, ξ and τ serve as a read-out of the water’s 1 H motion, given that the relative motion of the spin label is negligible compared to that of water. As discussed previously 13 , ξ and τ are sensitive to motions on both the picosecond (ps) and nanosecond (ns) timescales which on the protein surface correspond to DW and BW respectively. Thus, it is necessary to expand on the standard ODNP approach to separately analyze the ps and ns timescales of motion to access the DW and BW on the protein surface.…”

Section: Introductionmentioning

confidence: 90%

Spatially Heterogeneous Surface Water Diffusivity around Structured Protein Surfaces at Equilibrium

et al. 2017

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Hydration water on the surface of a protein is thought to mediate the thermodynamics of protein-ligand interaction. For hydration water to play a role beyond modulating global protein solubility or stability, the thermodynamic properties of hydration water must reflect on the properties of the heterogeneous protein surface, and thus spatially vary over the protein surface. A potent read-out of local variations in thermodynamic properties of hydration water is its equilibrium dynamics spanning picosecond to nanosecond timescales. In this study, we rely on Overhauser dynamic nuclear polarization (ODNP) to probe the equilibrium hydration water dynamics on the globular protein Chemotaxis Y (CheY), in dilute solution, at select sites located on the protein surface. ODNP reports on site-specific hydration dynamics within 5–10 Å of a label tethered to the biomolecular surface on two separate timescales of motion, corresponding to diffusive water (DW) and protein-water coupled motions referred to as bound water (BW). We find DW dynamics to be highly heterogeneous across the surface of CheY, while also finding significant populations of BW. We identify a significant correlation between DW dynamics and the local hydropathy of the CheY protein surface, as empirically determined by molecular dynamics (MD) simulations, and find the more hydrophobic sites to be hydrated with slower diffusing water. We furthermore compare the DW dynamics and BW population on the surface of CheY to that of another globular protein Annexin XII (Anx), two intrinsically disordered proteins (IDPs) ΔTau-187 and α-synuclein, CheY-inspired 5 residue peptides, polyproline-based peptides with systematic charge variation, and DPPC/DOPC liposomes. The DW dynamics on Anx is similarly heterogeneous as on CheY, and there is significant BW population on both Anx and CheY. In contrast, DW dynamics is relatively homogeneous on IDP and liposome surfaces, while BW is entirely absent. The heterogeneity in hydration water properties suggests that a structured protein surface has the capacity to encode information into its hydration water to mediate the free energy of interactions involving the protein surface.

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“…These ODNP parameters have been introduced previously and applied to a membrane protein and DNA (17,19,21). The analysis of these ODNP-derived relaxivities is particularly informative to account for the contribution of tightly or loosely bound water in the heterogeneous environment of a structured protein (19), as described in SI Overview of the ODNP Technique and the literature (17,21). Briefly, the cross-relaxivity k σ depends on the fluctuations of interactions at the ESR frequency (9.8 GHz), and therefore reports on fast water dynamics on the picosecond timescale.…”

Section: Morphologies and Accumulation Of Aggregation Intermediates Andmentioning

confidence: 99%

“…We have previously established a broadly applicable spectroscopic method, Overhauser dynamic nuclear polarizationenhanced NMR relaxometry (ODNP) (16,17), to probe changes in translational diffusivity of local water within 1 nm of nitroxide radical-based electron spin labels tethered to specific protein residues, and successfully reported on the study of protein folding, protein aggregation, and conformational changes of globular and membrane protein segments (18)(19)(20)(21). ODNP has revealed increased heterogeneity, i.e., dispersion, in local water diffusivity on the surface of a folded protein, compared with its unfolded counterpart or folding intermediate (20).…”

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confidence: 99%

Protein structural and surface water rearrangement constitute major events in the earliest aggregation stages of tau

Pavlova

Cheng

Kinnebrew

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Protein aggregation plays a critical role in the pathogenesis of neurodegenerative diseases, and the mechanism of its progression is poorly understood. Here, we examine the structural and dynamic characteristics of transiently evolving protein aggregates under ambient conditions by directly probing protein surface water diffusivity, local protein segment dynamics, and interprotein packing as a function of aggregation time, along the third repeat domain and C terminus of Δtau187 spanning residues 255-441 of the longest isoform of human tau. These measurements were achieved with a set of highly sensitive magnetic resonance tools that rely on sitespecific electron spin labeling of Δtau187. Within minutes of initiated aggregation, the majority of Δtau187 that is initially homogeneously hydrated undergoes structural transformations to form partially structured aggregation intermediates. This is reflected in the dispersion of surface water dynamics that is distinct around the third repeat domain, found to be embedded in an intertau interface, from that of the solvent-exposed C terminus. Over the course of hours and in a rate-limiting process, a majority of these aggregation intermediates proceed to convert into stable β-sheet structured species and maintain their stacking order without exchanging their subunits. The population of β-sheet structured species is >5% within 5 min of aggregation and gradually grows to 50-70% within the early stages of fibril formation, while they mostly anneal block-wisely to form elongated fibrils. Our findings suggest that the formation of dynamic aggregation intermediates constitutes a major event occurring in the earliest stages of tau aggregation that precedes, and likely facilitates, fibril formation and growth.biological water | soluble oligomers | amyloid formation | site-directed spin labeling | Alzheimer's disease

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Anomalously Rapid Hydration Water Diffusion Dynamics Near DNA Surfaces

Cited by 65 publications

References 77 publications

Hydration Dynamics of a Peripheral Membrane Protein

Hydration Dynamics of a Peripheral Membrane Protein

Spatially Heterogeneous Surface Water Diffusivity around Structured Protein Surfaces at Equilibrium

Protein structural and surface water rearrangement constitute major events in the earliest aggregation stages of tau

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