Dissociative mechanism for irreversible thermal denaturation of oligomeric proteins

Chebotareva, Natalia A.; Roman, Svetlana G.; Kurganov, B. I.

doi:10.1007/s12551-016-0220-z

Cited by 22 publications

(5 citation statements)

References 87 publications

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“…The negative effect of extreme physical and chemical parameters such as heat, cold, or high acidity, on the thermodynamic and kinetic stability of proteins is well known [30,31,32,33,34], and as stated before, many DFPPI organisms live in such extreme environments [17]. There is ample evidence that binding of partner subunits, and even small molecule ligands, cofactors and ions, often stabilize a protein from denaturation and proteasomal degradation [35,36,37,38].…”

Section: Available Evidence For the Translational Co-folding Centementioning

confidence: 99%

Dual-Family Peptidylprolyl Isomerases (Immunophilins) of Select Monocellular Organisms

Barik

2018

Biomolecules

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The dual-family peptidylprolyl cis-trans isomerases (immunophilins) represent a naturally occurring chimera of the classical FK506-binding protein (FKBP) and cyclophilin (CYN), connected by a flexible linker. They are found exclusively in monocellular organisms. The modular builds of these molecules represent two distinct types: CYN-(linker)-FKBP and FKBP-3TPR (tetratricopeptide repeat)-CYN. Abbreviated respectively as CFBP and FCBP, the two classes also exhibit distinct organism preference, the CFBP being found in prokaryotes, and the FCBP in eukaryotes. This review summarizes the mystery of these unique class of prolyl isomerases, focusing on their host organisms, potential physiological role, and likely routes of evolution.

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Section: Available Evidence For the Translational Co-folding Centementioning

confidence: 99%

Dual-Family Peptidylprolyl Isomerases (Immunophilins) of Select Monocellular Organisms

Barik

2018

Biomolecules

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“…The denaturation midpoint of a protein is defined as the temperature (T m ) or concentration of denaturant (C m ) at which both the folded and unfolded states are equally populated at equilibrium [ 43 ]. These parameters are expected to be altered in an oligomerized state [ 44 ]. Therefore, we next employed thermal and chemical denaturation assays to investigate the potential changes of T m and C m induced by oligomerization of TCP-25.…”

Section: Resultsmentioning

confidence: 99%

Concentration- and pH-Dependent Oligomerization of the Thrombin-Derived C-Terminal Peptide TCP-25

et al. 2020

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Peptide oligomerization dynamics affects peptide structure, activity, and pharmacodynamic properties. The thrombin C-terminal peptide, TCP-25 (GKYGFYTHVFRLKKWIQKVIDQFGE), is currently in preclinical development for improved wound healing and infection prevention. It exhibits turbidity when formulated at pH 7.4, particularly at concentrations of 0.3 mM or more. We used biochemical and biophysical approaches to explore whether the peptide self-associates and forms oligomers. The peptide showed a dose-dependent increase in turbidity as well as α-helical structure at pH 7.4, a phenomenon not observed at pH 5.0. By analyzing the intrinsic tryptophan fluorescence, we demonstrate that TCP-25 is more stable at high concentrations (0.3 mM) when exposed to high temperatures or a high concentration of denaturant agents, which is compatible with oligomer formation. The denaturation process was reversible above 100 µM of peptide. Dynamic light scattering demonstrated that TCP-25 oligomerization is sensitive to changes in pH, time, and temperature. Computational modeling with an active 18-mer region of TCP-25 showed that the peptide can form pH-dependent higher-order end-to-end oligomers and micelle-like structures, which is in agreement with the experimental data. Thus, TCP-25 exhibits pH- and temperature-dependent dynamic changes involving helical induction and reversible oligomerization, which explains the observed turbidity of the pharmacologically developed formulation.

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“…When discussing the thermal after-effect of UV irradiation of Ph b it is essential to note that this enzyme belongs to a class of oligomeric proteins, the unfolding of which is under the control of a conformational lock between neighboring subunits [ 42 , 43 ]. The conformational lock provides for a multi-step process of breakdown of the oligomeric structure at elevated temperatures.…”

Section: Discussionmentioning

confidence: 99%

A thermal after-effect of UV irradiation of muscle glycogen phosphorylase b

et al. 2017

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Different test systems are used to characterize the anti-aggregation efficiency of molecular chaperone proteins and of low-molecular-weight chemical chaperones. Test systems based on aggregation of UV-irradiated protein are of special interest because they allow studying the protective action of different agents at physiological temperatures. The kinetics of UV-irradiated glycogen phosphorylase b (UV-Phb) from rabbit skeletal muscle was studied at 37°C using dynamic light scattering in a wide range of protein concentrations. It has been shown that the order of aggregation with respect to the protein is equal to unity. A conclusion has been made that the rate-limiting stage of the overall process of aggregation is heat-induced structural reorganization of a UV-Phb molecule, which contains concealed damage.

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Dissociative mechanism for irreversible thermal denaturation of oligomeric proteins

Cited by 22 publications

References 87 publications

Dual-Family Peptidylprolyl Isomerases (Immunophilins) of Select Monocellular Organisms

Dual-Family Peptidylprolyl Isomerases (Immunophilins) of Select Monocellular Organisms

Concentration- and pH-Dependent Oligomerization of the Thrombin-Derived C-Terminal Peptide TCP-25

A thermal after-effect of UV irradiation of muscle glycogen phosphorylase b

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