High pressure effects on protein structure and function

Mozhaev, Vadim V.; Heremans, Karel; Frank, Johannes; Masson, Patrick; Balny, Claude

doi:10.1002/(sici)1097-0134(199601)24:1<81::aid-prot6>3.0.co;2-r

Cited by 672 publications

(471 citation statements)

References 53 publications

Supporting

Mentioning

431

Contrasting

Unclassified

Order By: Relevance

“…Pressure-induced hydration may help explain why many proteins undergo large changes in activity under pressure (32). Interactions between water and protein hydrophobic surfaces is particularly important for molecular interfaces in ligand or substrate binding and complex formation (33) and in multidomain protein folding (30).…”

Section: Resultsmentioning

confidence: 99%

Cooperative water filling of a nonpolar protein cavity observed by high-pressure crystallography and simulation

Collins

Hummer

Quillin

et al. 2005

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

192

213

View full text Add to dashboard Cite

Formation of a water-expelling nonpolar core is the paradigm of protein folding and stability. Although experiment largely confirms this picture, water buried in “hydrophobic” cavities is required for the function of some proteins. Hydration of the protein core has also been suggested as the mechanism of pressure-induced unfolding. We therefore are led to ask whether even the most nonpolar protein core is truly hydrophobic (i.e., water-repelling). To answer this question we probed the hydration of an ≈160-Å 3 , highly hydrophobic cavity created by mutation in T4 lysozyme by using high-pressure crystallography and molecular dynamics simulation. We show that application of modest pressure causes approximately four water molecules to enter the cavity while the protein itself remains essentially unchanged. The highly cooperative filling is primarily due to a small change in bulk water activity, which implies that changing solvent conditions or, equivalently, cavity polarity can dramatically affect interior hydration of proteins and thereby influence both protein activity and folding.

show abstract

Section: Resultsmentioning

confidence: 99%

Cooperative water filling of a nonpolar protein cavity observed by high-pressure crystallography and simulation

Collins

Hummer

Quillin

et al. 2005

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

192

213

View full text Add to dashboard Cite

show abstract

“…2,3 A variable which is less exploited is pressure, due to the greater demands of the experiments required. 4,5 However, it is well-known that high pressure tends to destabilize protein native structures, 6,7 indicative of a positive change of reaction volume for folding. A possible resolution of this initially counterintuitive effect 8 was proposed to be the existence of cavities within the folded protein, 9, 10 with substantial support for this hypothesis coming from experiments on cavityforming mutants.…”

Section: Introductionmentioning

confidence: 99%

Role of solvation in pressure-induced helix stabilization

Best

Miller

Mittal

2014

The Journal of Chemical Physics

View full text Add to dashboard Cite

In contrast to the well-known destabilization of globular proteins by high pressure, recent work has shown that pressure stabilizes the formation of isolated α-helices. However, all simulations to date have obtained a qualitatively opposite result within the experimental pressure range. We show that using a protein force field (Amber03w) parametrized in conjunction with an accurate water model (TIP4P/2005) recovers the correct pressure-dependence and an overall stability diagram for helix formation similar to that from experiment; on the other hand, we confirm that using TIP3P water results in a very weak pressure destabilization of helices. By carefully analyzing the contributing factors, we show that this is not merely a consequence of different peptide conformations sampled using TIP3P. Rather, there is a critical role for the solvent itself in determining the dependence of total system volume (peptide and solvent) on helix content. Helical peptide structures exclude a smaller volume to water, relative to non-helical structures with both the water models, but the total system volume for helical conformations is higher than non-helical conformations with TIP3P water at low to intermediate pressures, in contrast to TIP4P/2005 water. Our results further emphasize the importance of using an accurate water model to study protein folding under conditions away from standard temperature and pressure.

show abstract

“…Nevertheless, sufficiently high temperature may also distort protein structure and cause unfolding or denaturation (25-27). Another thermodynamic parameter, pressure, also plays an important role in protein structure and dynamics (28)(29)(30)(31)(32)(33). It changes the protein volume (33) and affects protein intermolecular and intramolecular structures explicitly (28,32).…”

mentioning

confidence: 99%

Effects of pressure on the dynamics of an oligomeric protein from deep-sea hyperthermophile

Shrestha

Bhowmik

Copley

et al. 2015

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

View full text Add to dashboard Cite

Inorganic pyrophosphatase (IPPase) from Thermococcus thioreducens is a large oligomeric protein derived from a hyperthermophilic microorganism that is found near hydrothermal vents deep under the sea, where the pressure is up to 100 MPa (1 kbar). It has attracted great interest in biophysical research because of its high activity under extreme conditions in the seabed. In this study, we use the quasielastic neutron scattering (QENS) technique to investigate the effects of pressure on the conformational flexibility and relaxation dynamics of IPPase over a wide temperature range. The β-relaxation dynamics of proteins was studied in the time ranges from 2 to 25 ps, and from 100 ps to 2 ns, using two spectrometers. Our results indicate that, under a pressure of 100 MPa, close to that of the native environment deep under the sea, IPPase displays much faster relaxation dynamics than a mesophilic model protein, hen egg white lysozyme (HEWL), at all measured temperatures, opposite to what we observed previously under ambient pressure. This contradictory observation provides evidence that the protein energy landscape is distorted by high pressure, which is significantly different for hyperthermophilic (IPPase) and mesophilic (HEWL) proteins. We further derive from our observations a schematic denaturation phase diagram together with energy landscapes for the two very different proteins, which can be used as a general picture to understand the dynamical properties of thermophilic proteins under pressure.protein dynamics | energy landscape | denaturation phase diagram | quasielastic neutron scattering | mode coupling theory T he biological functions of proteins, such as enzyme catalysis, are often understood from their crystallographic structures (1). On the other hand, it is crucial to take into account dynamic behavior to fully comprehend these functions (2, 3). In vivo, proteins are in constant motion among different conformations (3-5). The thermal energy, which is of the order of k B T per atom, where k B is the Boltzmann constant and T is the absolute temperature, triggers biomolecules to sample different conformations around the average structure. These conformations are also known as conformational substates (CSs) (5). Fluctuations among these CSs play an important role in protein function (3,5). These lead to the concept of a multidimensional potential energy landscape (EL) that specifies a complete description of CSs in proteins (6-9). The existence of an EL was proposed by H. Frauenfelder and others in the 1970s and has been validated both by computations and by experiments (6-12).Proteins show various dynamic phenomena over a wide range of timescales, from picoseconds to milliseconds (13). A fast dynamic process, on a timescale of a picosecond to 10 ns, also known as β-relaxation, occurs due to small amplitude fluctuations in atoms/ molecules, such as loop motions and side-chain rotations (14). The energy barrier or activation energy (E A ) between different CSs for this process is smaller than k B T (15). On t...

show abstract

High pressure effects on protein structure and function

Abstract: Many biochemists would regard pressure as a physical parameter mainly of theoretical interest and of rather limited value in experimental biochemistry. The goal of this overview is to show that pressure is a powerful tool for the study of proteins and modulation of enzymatic activity.

Cited by 672 publications

References 53 publications

Cooperative water filling of a nonpolar protein cavity observed by high-pressure crystallography and simulation

Cooperative water filling of a nonpolar protein cavity observed by high-pressure crystallography and simulation

Role of solvation in pressure-induced helix stabilization

Effects of pressure on the dynamics of an oligomeric protein from deep-sea hyperthermophile

Contact Info

Product

Resources

About