Distinct Conformational States of the Alzheimer β‐Amyloid Peptide Can Be Detected by High‐Pressure NMR Spectroscopy

Munte, Cláudia Elisabeth; Erlach, Markus Beck; Kremer, Werner; Koehler, Joerg; Kalbitzer, Hans Robert

doi:10.1002/anie.201301537

Cited by 36 publications

(59 citation statements)

References 31 publications

(44 reference statements)

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“…[12] Furthermore, advancements in high-resolution, high-pressure probe design [13][14][15] have not only allowed for the study of geochemical reaction dynamics, [16][17][18] but also the pressure dependencies of critical micelle concentrations, [19] dissolved gas formation from catalytic reactions, [20] as well as several studies probing protein folding, aggregation, and stabilization of rare highenergy states. [21][22][23][24] Despite the tremendous scientific advancement from these studies, the current NMR probe designs cannot fully accommodate both high pressures and highresolution molecular-level data needed to begin to evaluate the geochemical models.…”

mentioning

confidence: 99%

A High‐Pressure NMR Probe for Aqueous Geochemistry

Pautler¹,

Colla²,

Johnson³

et al. 2014

Angew Chem Int Ed

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A non-magnetic piston-cylinder pressure cell is presented for solution-state NMR spectroscopy at geochemical pressures. The probe has been calibrated up to 20 kbar using in situ ruby fluorescence and allows for the measurement of pressure dependencies of a wide variety of NMR-active nuclei with as little as 10 μL of sample in a microcoil. Initial (11)B NMR spectroscopy of the H3BO3-catechol equilibria reveals a large pressure-driven exchange rate and a negative pressure-dependent activation volume, reflecting increased solvation and electrostriction upon boron-catecholate formation. The inexpensive probe design doubles the current pressure range available for solution NMR spectroscopy and is particularly important to advance the field of aqueous geochemistry.

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confidence: 99%

A High‐Pressure NMR Probe for Aqueous Geochemistry

Pautler¹,

Colla²,

Johnson³

et al. 2014

Angew Chem Int Ed

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“…The significance of this observation is that the different conformations of Ras are all potential drug targets, because stabilisation of Ras in one form has important effects on Ras-dependent signalling pathways. The same is of course true for many other proteins that display allosteric behaviour, and indeed high pressure has been suggested as a way of identifying drug targets for several of these [62,[111][112][113].…”

Section: Dynamic Allostery?mentioning

confidence: 90%

Characterization of low-lying excited states of proteins by high-pressure NMR

Williamson

Kitahara

2019

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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Hydrostatic pressure alters the free energy of proteins by a few kJ mol-1 , with the amount depending on their partial molar volumes. Because the folded ground state of a protein contains cavities, it is always a state of large partial molar volume. Therefore pressure always destabilises the ground state and increases the population of partially and completely unfolded states. This is a mild and reversible conformational change, which allows the study of excited states under thermodynamic equilibrium conditions. Many of the excited states studied in this way are functionally relevant; they also seem to be very similar to kinetic folding intermediates, thus suggesting that evolution has made use of the T includes features such as ligand binding, structural change during the catalytic cycle, and dynamic allostery.

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“…This might have a distinct advantage over the other denaturation methods in terms of reversibility. Rare "excited" conformational states, for example, intermediates on the pathway to amyloid fibrils that have a relative population of as small as 0.0005 at ambient pressure, can be stabilized by pressure and thus detected [103,104]. Other advantages of high-pressure NMR for the study of protein folding, protein aggregation, and ligand interactions at molecular resolution have been reviewed [105].…”

Section: Advances In Multidimensional Real-time Nmr Spectroscopymentioning

confidence: 99%