The Thermal Structural Transition of α-Crystallin Inhibits the Heat Induced Self-Aggregation

Maulucci, Giuseppe; Papi, Massimiliano; Arcòvito, Giuseppe; Spirito, Marco De

doi:10.1371/journal.pone.0018906

Cited by 14 publications

(26 citation statements)

References 39 publications

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“… obtained in the previous article [18] were 33,8 and 137,6 kcal/mol, and are refined in this model, where temperature dependent underestimation of rate constant doesn't occur.…”

Section: Resultsmentioning

confidence: 86%

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The Thermal Structural Transition of Alpha-Crystallin Modulates Subunit Interactions and Increases Protein Solubility

et al. 2012

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BackgroundAlpha crystallin is an oligomer composed of two types of subunits, alpha-A and alpha-B crystallin, and is the major constituent of human lens. The temperature induced condensation of alpha-crystallin, the main cause for eye lens opacification (cataract), is a two step-process, a nucleation followed by an aggregation phase, and a protective effect towards the aggregation is exhibited over the alpha crystallin phase transition temperature (Tc = 318.16 K).Methods/ResultsTo investigate if a modulation of the subunit interactions over Tc could trigger the protective mechanism towards the aggregation, we followed, by using simultaneously static and dynamic light scattering, the temperature induced condensation of alpha-crystallin. By developing a mathematical model able to uncouple the nucleation and aggregation processes, we find a previously unobserved transition in the nucleation rate constant. Its temperature dependence allows to determine fundamental structural parameters, the chemical potential (Δμ) and the interfacial tension (γ) of the aggregating phase, that characterize subunit interactions.Conclusions/General SignificanceThe decrease of both Δμ and γ at Tc, and a relative increase in solubility, reveal a significative decrease in the strenght of alpha-crystallin subunits interactions, which protects from supramolecolar condensation in hypertermic conditions. On the whole, we suggest a general approach able to understand the structural and kinetic mechanisms involved in aggregation-related diseases and in drugs development and testing.

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“… obtained in the previous article [18] were 33,8 and 137,6 kcal/mol, and are refined in this model, where temperature dependent underestimation of rate constant doesn't occur.…”

Section: Resultsmentioning

confidence: 86%

“…(17), and of the Rayleigh Ratios I (q) , measured at θ = 90°, not reported in [18]. The results for samples at different temperatures above Tc = 318.16 K, are shown in Figure 2a–b.…”

Section: Resultsmentioning

confidence: 99%

The Thermal Structural Transition of Alpha-Crystallin Modulates Subunit Interactions and Increases Protein Solubility

et al. 2012

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“…At 45 °C, the transition has been shown to be biologically relevant [ 46 ]. At this temperature, α-crystallin undergoes minor changes in its tertiary structure as its hydrophobic surface is exposed [ 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

“…It was reported that Aβ was detected in the lens nucleus and deep lens fiber cells [ 48 , 49 , 50 , 51 ]. Aβ in the lens is produced by peptide degradation from APP.…”

Section: Discussionmentioning

confidence: 99%

Effect of a Lens Protein in Low-Temperature Culture of Novel Immortalized Human Lens Epithelial Cells (iHLEC-NY2)

Yamamoto

Takeda

Hatsusaka

et al. 2020

Cells

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The prevalence of nuclear cataracts was observed to be significantly higher among residents of tropical and subtropical regions compared to those of temperate and subarctic regions. We hypothesized that elevated environmental temperatures may pose a risk of nuclear cataract development. The results of our in silico simulation revealed that in temperate and tropical regions, the human lens temperature ranges from 35.0 °C to 37.5 °C depending on the environmental temperature. The medium temperature changes during the replacement regularly in the cell culture experiment were carefully monitored using a sensor connected to a thermometer and showed a decrease of 1.9 °C, 3.0 °C, 1.7 °C, and 0.1 °C, after 5 min when setting the temperature of the heat plate device at 35.0 °C, 37.5 °C, 40.0 °C, and 42.5 °C, respectively. In the newly created immortalized human lens epithelial cell line clone NY2 (iHLEC-NY2), the amounts of RNA synthesis of αA crystallin, protein expression, and amyloid β (Aβ)1-40 secreted into the medium were increased at the culture temperature of 37.5 °C compared to 35.0 °C. In short-term culture experiments, the secretion of Aβ1-40 observed in cataracts was increased at 37.5 °C compared to 35.0 °C, suggesting that the long-term exposure to a high-temperature environment may increase the risk of cataracts.

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“…Generally, upon heating, a-crystallin undergoes structural changes resulting in increased exposure of additional hydrophobic sites associated with increased CLA [1,[20][21][22]28,29]. Once exposed to high temperatures, the protein upon cooling does not return to its original conformational state but adopts a conformation characterized by increased surface hydrophobicity and molecular mass (aggregate size) [1,[29][30][31]. This increase in CLA of a-crystallin upon structural perturbation is mediated by aAbut not aB crystallin.…”

Section: Discussionmentioning

confidence: 99%

Temperature-dependent structural and functional properties of a mutant (F71L) αA-crystallin: Molecular basis for early onset of age-related cataract

Validandi¹,

Reddy²,

Srinivas³

et al. 2011

FEBS Letters

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Previously we identified a novel mutation (F71L) in the αA-crystallin gene associated with early onset of age-related cataract. However, it is not known how the missense substitution translates into reduced chaperone-like activity (CLA), and how the structural and functional changes lead to early onset of the disease. Herein, we show that under native conditions the F71L-mutant is not significantly different from wild-type with regard to secondary and tertiary structural organization, hydrophobicity and the apparent molecular mass of oligomer but has substantial differences in structural and functional properties following a heat treatment. Wild-type αA-crystallin demonstrated increased CLA, whereas the F71L-mutant substantially lost its CLA upon heat treatment. Further, unlike the wild-type αA-subunit, F71L-subunit did not protect the αB-subunit in hetero-oligomeric complex from heat-induced aggregation. Moreover, hetero-oligomer containing F71L and αB in 3:1 ratio had significantly lower CLA upon thermal treatment compared to its unheated control. These results indicate that α-crystallin complexes containing F71L-αA subunits are less stable and have reduced CLA. Therefore, F71L may lead to earlier onset of cataract due to interaction with several environmental factors (e.g., temperature in this case) along with the aging process.

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The Thermal Structural Transition of α-Crystallin Inhibits the Heat Induced Self-Aggregation

Cited by 14 publications

References 39 publications

The Thermal Structural Transition of Alpha-Crystallin Modulates Subunit Interactions and Increases Protein Solubility

The Thermal Structural Transition of Alpha-Crystallin Modulates Subunit Interactions and Increases Protein Solubility

Effect of a Lens Protein in Low-Temperature Culture of Novel Immortalized Human Lens Epithelial Cells (iHLEC-NY2)

Temperature-dependent structural and functional properties of a mutant (F71L) αA-crystallin: Molecular basis for early onset of age-related cataract

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