Direct observation of hierarchical protein dynamics

Lewandowski, Józef; Halse, Meghan E.; Blackledge, Martin; Emsley, Lyndon

doi:10.1126/science.aaa6111

Cited by 233 publications

(316 citation statements)

References 75 publications

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“…In variable temperature 1 H and 13 C MAS ssNMR measurements we detected the temperatures at which the solvent froze and the liquid-to-gel transition of the lipids occurred. In line with earlier MAS ssNMR studies (40)(41)(42)(43), the aqueous solvent (20 mM HEPES buffer at pH 7.4) froze at temperatures significantly lower than 0 C. This effect stems from the reduced length scales of water pockets in the sample, compared with bulk water that freezes at 0 C (see Discussion). To our surprise, we also noted a substantial lowering of the lipid phase transition.…”

Section: Mas Nmr Probing Of Solvents and Lipid Dynamicssupporting

confidence: 83%

“…2 C), the water peak moves (in accordance to the known temperature dependence of water 1 H shifts (35,36)), but remains intense and narrow. Thus, the water remains unfrozen even at À9 C. As is discussed in more detail below, this kind of solvent freezing point depression is typically seen for densely packed MAS ssNMR samples (29,42,43). Consistent with the T m values of the DOPC and TOCL lipids, which are well below 0 C (Fig.…”

Section: Phase Changes In Monounsaturated Mixed-lipid Vesiclessupporting

confidence: 64%

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MAS 1 H NMR Probes Freezing Point Depression of Water and Liquid-Gel Phase Transitions in Liposomes

Mandal

Wel

2016

Biophysical Journal

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The lipid bilayer typical of hydrated biological membranes is characterized by a liquid-crystalline, highly dynamic state. Upon cooling or dehydration, these membranes undergo a cooperative transition to a rigidified, more-ordered, gel phase. This characteristic phase transition is of significant biological and biophysical interest, for instance in studies of freezing-tolerant organisms. Magic-angle-spinning (MAS) solid-state NMR (ssNMR) spectroscopy allows for the detection and characterization of the phase transitions over a wide temperature range. In this study we employ MAS 1 H NMR to probe the phase transitions of both solvent molecules and different hydrated phospholipids, including tetraoleoyl cardiolipin (TOCL) and several phosphatidylcholine lipid species. The employed MAS NMR sample conditions cause a previously noted substantial reduction in the freezing point of the solvent phase. The effect on the solvent is caused by confinement of the aqueous solvent in the small and densely packed MAS NMR samples. In this study we report and examine how the freezing point depression also impacts the lipid phase transition, causing a ssNMR-observed reduction in the lipids' melting temperature (T m ). The molecular underpinnings of this phenomenon are discussed and compared with previous studies of membrane-associated water phases and the impact of membrane-protective cryoprotectants.

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Section: Mas Nmr Probing Of Solvents and Lipid Dynamicssupporting

confidence: 83%

Section: Phase Changes In Monounsaturated Mixed-lipid Vesiclessupporting

confidence: 64%

MAS 1 H NMR Probes Freezing Point Depression of Water and Liquid-Gel Phase Transitions in Liposomes

Mandal

Wel

2016

Biophysical Journal

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“…Typically, X-ray crystallographic data are measured from crystals maintained at 100 K in order to immobilize X-raygenerated free radicals and damaged protein and minimize radiation damage, leading an increase in crystal lifetime of up to two orders of magnitude relative to RT (Southworth-Davies et al, 2007). Between RT and 100 K, protein crystals undergo at least one and possibly several temperature-dependent transitions (Weik & Colletier, 2010;Lewandowski et al, 2015;Ringe & Petsko, 2003;Keedy et al, 2015). Notably, anharmonic macromolecular motions resume above the glass transition that occurs in the range 180-220 K, where solvent viscosity is greatly reduced.…”

Section: Introductionmentioning

confidence: 99%

Active-site protein dynamics and solvent accessibility in nativeAchromobacter cycloclastescopper nitrite reductase

Sen

Horrell

Kekilli

et al. 2017

Int Union Crystallogr J

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Microbial nitrite reductases are denitrifying enzymes that are a major component of the global nitrogen cycle. Multiple structures measured from one crystal (MSOX data) of copper nitrite reductase at 240 K, together with molecular-dynamics simulations, have revealed protein dynamics at the type 2 copper site that are significant for its catalytic properties and for the entry and exit of solvent or ligands to and from the active site. Molecular-dynamics simulations were performed using different protonation states of the key catalytic residues (Asp CAT and His CAT ) involved in the nitrite-reduction mechanism of this enzyme. Taken together, the crystal structures and simulations show that the Asp CAT protonation state strongly influences the active-site solvent accessibility, while the dynamics of the active-site 'capping residue' (Ile CAT ), a determinant of ligand binding, are influenced both by temperature and by the protonation state of Asp CAT . A previously unobserved conformation of Ile CAT is seen in the elevated temperature series compared with 100 K structures. DFT calculations also show that the loss of a bound water ligand at the active site during the MSOX series is consistent with reduction of the type 2 Cu atom.

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“…However, the barriers need to be small to make their crossing possible at physiological temperature, as the dynamics are "fueled" by the thermal fluctuations of the surrounding liquid. [20,21] Experimentally it has been observed that upon binding the loss in entropy of the protein, which would oppose the reaction, is often paired to the emergence of disorder in remote regions of the protein, apparently uncorrelated to the binding site. [19] New flexible regions often arise in the relaxed bound state, or exposed hydrophobic residues are found to transition to the hydrophobic region, becoming protected and increasing the entropy of the solvent in the well-known mechanism of enthalpy-entropy compensation.…”

Section: Introductionmentioning

confidence: 99%

Mode localization in the cooperative dynamics of protein recognition

Copperman

Guenza

2016

The Journal of Chemical Physics

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The biological function of proteins is encoded in their structure and expressed through the mediation of their dynamics. Local fluctuations are known to initiate biologically relevant pathways as they cooperatively enhance the dynamics in specific regions in the protein. Those biologically active regions provide energetically-comparable conformational states that can be trapped by a reacting partner. We analyze this mechanism as we calculate the dynamics of monomeric and dimerized HIV protease, and free Insulin Growth Factor II Receptor (IGF2R) domain 11 and its IGF2R:IGF2 complex. We adopt a newly developed coarse-grained model, the Langevin Equation for Protein Dynamics (LE4PD), which predicts dynamical relevant mechanisms with high accuracy. Both simulation-derived and experimental NMR conformers are the input structural ensembles for the LE4PD. The use of the experimental NMR conformers requires minimal computational resources.

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Direct observation of hierarchical protein dynamics

Cited by 233 publications

References 75 publications

MAS 1 H NMR Probes Freezing Point Depression of Water and Liquid-Gel Phase Transitions in Liposomes

MAS 1 H NMR Probes Freezing Point Depression of Water and Liquid-Gel Phase Transitions in Liposomes

Active-site protein dynamics and solvent accessibility in nativeAchromobacter cycloclastescopper nitrite reductase

Mode localization in the cooperative dynamics of protein recognition

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