Effects of osmolytes on protein-solvent interactions in crowded environment: Analyzing the effect of TMAO on proteins in crowded solutions

Breydo, Leonid; Sales, Aldo Torres; Ferreira, Luísa A.; Fedotoff, Olga; Shevelyova, Marina P.; Permyakov, Sergei E.; Kroeck, Kyle G.; Permyakov, Eugene A.; Zaslavsky, Boris Y.; Uversky, Vladimir N.

doi:10.1016/j.abb.2015.02.021

Cited by 19 publications

(21 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was shown that osmolytes under conditions of molecular crowding, as a rule, promote compaction of protein structure, increase protein stability, and prevent their aggregation. Thus, overall, osmolyte function on proteins under conditions of molecular crowding is generally the same as in buffer solutions of low salinity [63,[108][109][110][111][112][113][114]. It should be noted that under the conditions of molecular crowding, structures of internally disordered proteins do not undergo significant changes [115,116], which indicates that the excluded volume effect does not play a significant role in the process of osmolyte interactions with proteins.…”

Section: Osmolytes and Native Internally-disordered Proteins; Osmolytesmentioning

confidence: 97%

Protein folding and stability in the presence of osmolytes

et al. 2016

View full text Add to dashboard Cite

Osmolytes are molecules whose function, among others, is to balance the hydrostatic pressure between the intracellular and extracellular compartments. Accumulation of osmolytes in a cell occurs in response to stress caused by changes in pressure, temperature, pH, or the concentration of inorganic salts. Osmolytes can prevent the denaturation of native proteins and promote the renaturation of unfolded proteins. Investigation of the roles of osmolyte in these processes is essential for our understanding of the mechanisms of protein folding and function in vivo. The large number of published reports that have been devoted to the effects of osmolytes on proteins are not always consistent with each other. In this review, an attempt is made to systemize the array of data on this subject and to consider the problem of protein folding and stability in osmolyte solutions from a single viewpoint.

show abstract

Section: Osmolytes and Native Internally-disordered Proteins; Osmolytesmentioning

confidence: 97%

Protein folding and stability in the presence of osmolytes

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Macromolecules account for about 40% of cell volume; thus all intracellular reagents are greatly concentrated, with both favorable and unfavorable effects on protein folding [21–23]. The pro-folding effects of organic osmolytes may be intensified in the already molecularly crowded conditions of a cell [24]. With respect to signal transduction pathways, molecular crowding is potentially of great significance [25].…”

Section: Discussionmentioning

confidence: 99%

Restored mutant receptor:Corticoid binding in chaperone complexes by trimethylamine N-oxide

et al. 2017

View full text Add to dashboard Cite

Without a glucocorticoid (GC) ligand, the transcription factor glucocorticoid receptor (GR) is largely cytoplasmic, with its GC-binding domain held in high affinity conformation by a cluster of chaperones. Binding a GC causes serial dis- and re-associations with chaperones, translocation of the GR to the nucleus, where it binds to DNA sites and associates with coregulatory proteins and basic transcription complexes. Herein, we describe the effects of a potent protective osmolyte, trimethylamine N-oxide (TMAO), on a conditions-dependent “activation-labile” mutant GR (GRact/l), which under GR-activating conditions cannot bind GCs in cells or in cell cytosols. In both cells and cytosols, TMAO restores binding to GRact/l by stabilizing it in complex with chaperones. Cells bathed in much lower concentrations of TMAO than those required in vitro show restoration of GC binding, presumably due to intracellular molecular crowding effects.

show abstract

“…Once Δπ*, Δα, Δβ, and c parameters in multiple ATPSs are determined, the solute specific coefficients are calculated by multiple linear regression analysis using Eq. 21,22 and sorbitol -this work). The partition coefficient of a compound with pre-determined solute specific coefficients in a "new" ATPS with established solvent properties of the phases can be predicted with 90-95% accuracy.…”

Section: Introductionmentioning

confidence: 87%

“…Figure 2 shows the dependence of logarithms of partition coefficients K (i) DNP-AA for sodium salts of DNP-amino acids in dextran-PEG-0.01 M K/NaPB ATPS with and without 0.5 M osmolyte (sorbitol, sucrose, trehalose, and TMAO 21,22 ) on the length of the aliphatic side-chain of DNP-amino acid expressed in equivalent number of CH 2 groups, N C. In each case, the observed dependence is linear and can be described as: Figure 2 shows the dependence of logarithms of partition coefficients K (i) DNP-AA for sodium salts of DNP-amino acids in dextran-PEG-0.01 M K/NaPB ATPS with and without 0.5 M osmolyte (sorbitol, sucrose, trehalose, and TMAO 21,22 ) on the length of the aliphatic side-chain of DNP-amino acid expressed in equivalent number of CH 2 groups, N C. In each case, the observed dependence is linear and can be described as:…”

Section: Solvent Properties Of the Atps Phasesmentioning

confidence: 99%

“…3,4 According to this model, the aqueous osmolyte solution is a media unfavorable for the unfolded forms of globular proteins. We previously reported analysis of the effects of sucrose, trehalose, and TMAO on protein-water interactions using the solvent interaction analysis (SIA), 21,22 which is based on analytical application of partitioning of solutes in aqueous two-phase systems (ATPSs). [5][6][7][8][9] Solubility and other physicochemical properties of various other compounds are known to be affected in solutions of different osmolytes in the osmolyte-specific manner.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Analyzing the effects of protecting osmolytes on solute–water interactions by solvatochromic comparison method: I. Small organic compounds

et al. 2015

Self Cite

View full text Add to dashboard Cite

Solvent properties of water (dipolarity/polarizability, hydrogen bond donor (HBD) acidity, and hydrogen bond acceptor (HBA) basicity) in aqueous solutions of osmolytes (sorbitol, sucrose, trehalose, and trimethylamine N-oxide (TMAO)) were studied at different osmolytes concentrations using solvatochromic comparison method. The solvent properties of aqueous media in the coexisting phases of aqueous dextran-PEG-sodium/potassium phosphate buffer (0.01 M K/NaPB, pH7.4) two-phase system (ATPS) containing 0.5 M osmolyte additive (sorbitol, sucrose, trehalose, TMAO) and osmolytefree ATPS were characterized. Partitioning of 30 low molecular weight polar organic compounds was examined in aqueous dextran-PEG-0.01M K/NaPB ATPS containing 0.5 M sorbitol. The solute-specific coefficients for the compounds examined were determined from the data obtained here and those reported previously. The results obtained demonstrate that the osmolytes examined affect the partition behavior of organic compounds in ATPS by influencing solvent properties of the media and not by direct association with the compounds. 23 ATPSs are formed in aqueous mixtures of different polymers or a single polymer and a specific salt. 24,25 When two certain polymers, for example, dextran and Ficoll, are mixed in water above certain concentrations, the mixture separates into two

show abstract

Effects of osmolytes on protein-solvent interactions in crowded environment: Analyzing the effect of TMAO on proteins in crowded solutions

Cited by 19 publications

References 46 publications

Protein folding and stability in the presence of osmolytes

Protein folding and stability in the presence of osmolytes

Restored mutant receptor:Corticoid binding in chaperone complexes by trimethylamine N-oxide

Analyzing the effects of protecting osmolytes on solute–water interactions by solvatochromic comparison method: I. Small organic compounds

Contact Info

Product

Resources

About