Spectroscopic studies of the unfolding of a multimeric protein α‐crystallin

Chowdhury, Aritra; Choudhury, Aparajita; Banerjee, Victor; Banerjee, Rajat; Das, K. P.

doi:10.1002/bip.22417

Cited by 7 publications

(2 citation statements)

References 51 publications

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“…The D h of α-crystallin at the maximum concentration of urea was 7.0 ± 0.8 nm, and the particle D h of HMWA at the maximum concentration of urea was 8.0 ± 1.2 nm. This is consistent with the literature data [30,39]. The molecular mass of such particles, calculated for a linear polymer, is 20-22 kDa.…”

Section: Resultssupporting

confidence: 92%

Refolding Increases the Chaperone-like Activity of αH-Crystallin and Reduces Its Hydrodynamic Diameter to That of α-Crystallin

Muranov,

Poliansky,

Borzova

et al. 2023

IJMS

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αH-Crystallin, a high molecular weight form of α-crystallin, is one of the major proteins in the lens nucleus. This high molecular weight aggregate (HMWA) plays an important role in the pathogenesis of cataracts. We have shown that the chaperone-like activity of HMWA is 40% of that of α-crystallin from the lens cortex. Refolding with urea significantly increased—up to 260%—the chaperone-like activity of α-crystallin and slightly reduced its hydrodynamic diameter (Dh). HMWA refolding resulted in an increase in chaperone-like activity up to 120% and a significant reduction of Dh of protein particles compared with that of α-crystallin. It was shown that the chaperone-like activity of HMWA, α-crystallin, and refolded α-crystallin but not refolded HMWA was strongly correlated with the denaturation enthalpy measured with differential scanning calorimetry (DSC). The DSC data demonstrated a significant increase in the native protein portion of refolded α-crystallin in comparison with authentic α-crystallin; however, the denaturation enthalpy of refolded HMWA was significantly decreased in comparison with authentic HMWA. The authors suggested that the increase in the chaperone-like activity of both α-crystallin and HMWA could be the result of the correction of misfolded proteins during renaturation and the rearrangement of protein supramolecular structures.

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Section: Resultssupporting

confidence: 92%

Refolding Increases the Chaperone-like Activity of αH-Crystallin and Reduces Its Hydrodynamic Diameter to That of α-Crystallin

Muranov,

Poliansky,

Borzova

et al. 2023

IJMS

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“…It is shown in [ 30 ] that although the optimal pH for the functioning of alpha-B-crystallin lies in the range from 7 to 8, even at acidic pH this chaperone inhibits the growth of amyloid fibrils formed from Abeta-peptide and beta-2-microglobulin. In this regard, to simulate stress conditions that do not inhibit the activity of the chaperone and, at the same time, induce the formation of amyloid fibrils, we decided to increase the acidity of the solution to pH 2 [ 44 , 67 ]. It should be noted that a low pH is characteristic of organs where amyloid fibrils studied by us are accumulated (kidney, stomach, intestines, etc.)…”

Section: Resultsmentioning

confidence: 99%

Alpha-B-Crystallin Effect on Mature Amyloid Fibrils: Different Degradation Mechanisms and Changes in Cytotoxicity

Stepanenko

Sulatsky

Михайлова

et al. 2020

IJMS

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Given the ability of molecular chaperones and chaperone-like proteins to inhibit the formation of pathological amyloid fibrils, the chaperone-based therapy of amyloidosis has recently been proposed. However, since these diseases are often diagnosed at the stages when a large amount of amyloids is already accumulated in the patient’s body, in this work we pay attention to the undeservedly poorly studied problem of chaperone and chaperone-like proteins’ effect on mature amyloid fibrils. We showed that a heat shock protein alpha-B-crystallin, which is capable of inhibiting fibrillogenesis and is found in large quantities as a part of amyloid plaques, can induce degradation of mature amyloids by two different mechanisms. Under physiological conditions, alpha-B-crystallin induces fluffing and unweaving of amyloid fibrils, which leads to a partial decrease in their structural ordering without lowering their stability and can increase their cytotoxicity. We found a higher correlation between the rate and effectiveness of amyloids degradation with the size of fibrils clusters rather than with amino acid sequence of amyloidogenic protein. Some external effects (such as an increase in medium acidity) can lead to a change in the mechanism of fibrils degradation induced by alpha-B-crystallin: amyloid fibers are fragmented without changing their secondary structure and properties. According to recent data, fibrils cutting can lead to the generation of seeds for new bona fide amyloid fibrils and accelerate the accumulation of amyloids, as well as enhance the ability of fibrils to disrupt membranes and to reduce cell viability. Our results emphasize the need to test the chaperone effect not only on fibrillogenesis, but also on the mature amyloid fibrils, including stress conditions, in order to avoid undesirable disease progression during chaperone-based therapy.

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