Oligomeric state of αB-crystallin under crowded conditions

Chebotareva, Natalia A.; Eronina, Tatiana B.; Roman, Svetlana G.; Mikhaylova, Valeriya V.; Sluchanko, Nikolai N.; Gusev, Nikolai B.; Bi, Kurganov

doi:10.1016/j.bbrc.2018.12.015

Cited by 9 publications

(19 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This also indicates the interaction between the chaperone and the target protein under crowded conditions. Although we cannot obtain the sedimentation behavior of HSPB5 itself at the concentrations used, according to our earlier data HSPB5 appears to dissociate at elevated temperature in a concentration dependent manner [ 25 , 32 ]. Thus, HSPB5 may be in a dissociated form (dimeric or monomeric) at such low concentrations in a buffer solution.…”

Section: Resultsmentioning

confidence: 99%

“…HSPB5 tends to form large polydisperse assemblies ranging from 10-mer to 40-mer and higher, having very dynamic structures [ 19 , 23 , 24 , 25 ]. All oligomeric forms possess chaperone-like activity and easily exchange their subunits [ 20 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is well accepted that a flexible dynamic quaternary structure is necessary for sHSPs activity [ 1 , 4 , 10 , 28 ]. Changes in the cellular environment, such as temperature [ 9 , 10 , 27 , 29 ], pH [ 30 ], the presence of ions [ 31 , 32 ], post-translational modification (phosphorylation) [ 33 , 34 , 35 ], redox environment [ 7 , 30 ] and crowding [ 19 , 25 , 32 , 36 , 37 , 38 ] also regulate chaperone activity by affecting the structural and oligomerization dynamics of sHSPs [ 4 , 5 ]. It has been reported that sHSP dynamics is a very complex process that includes five levels of regulation: (1) flexible domains flanking the ACD, (2) polydisperse self-oligomerization, (3) hetero- oligomerization with other sHSPs, (4) subunit exchange, and (5) regulation by the cellular environment [ 5 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

“…Since it has a strong effect on protein–protein interactions, it should affect the conformation and self-association of the chaperone, the interaction of the chaperone with the target protein, and the aggregation of the target protein. Previously, we have shown by the analytical ultracentrifugation (AUC) method that crowding strongly affects the oligomeric state of HSPB5, HSPB6, HSPB1 and α-crystallin [ 25 , 32 , 36 , 61 , 62 , 63 , 64 ]. Thus, one might assume that crowding affects the capability of sHSPs to prevent aggregation of target proteins.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Chaperone-Like Activity of HSPB5: The Effects of Quaternary Structure Dynamics and Crowding

Chebotareva

Roman

Borzova

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Small heat-shock proteins (sHSPs) are ATP-independent molecular chaperones that interact with partially unfolded proteins, preventing their aberrant aggregation, thereby exhibiting a chaperone-like activity. Dynamics of the quaternary structure plays an important role in the chaperone-like activity of sHSPs. However, relationship between the dynamic structure of sHSPs and their chaperone-like activity remains insufficiently characterized. Many factors (temperature, ions, a target protein, crowding etc.) affect the structure and activity of sHSPs. The least studied is an effect of crowding on sHSPs activity. In this work the chaperone-like activity of HSPB5 was quantitatively characterized by dynamic light scattering using two test systems, namely test systems based on heat-induced aggregation of muscle glycogen phosphorylase b (Phb) at 48 °C and dithiothreitol-induced aggregation of α-lactalbumin at 37 °C. Analytical ultracentrifugation was used to control the oligomeric state of HSPB5 and target proteins. The possible anti-aggregation functioning of suboligomeric forms of HSPB5 is discussed. The effect of crowding on HSPB5 anti-aggregation activity was characterized using Phb as a target protein. The duration of the nucleation stage was shown to decrease with simultaneous increase in the relative rate of aggregation of Phb in the presence of HSPB5 under crowded conditions. Crowding may subtly modulate sHSPs activity.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Chaperone-Like Activity of HSPB5: The Effects of Quaternary Structure Dynamics and Crowding

Chebotareva

Roman

Borzova

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the lens, protein concentrations of 100-400 mg/mL generate a highly crowded milieu, whereas structural investigations in vitro are often performed in low µM ranges [140,141]. Recently, in a comparative approach for αB, a decrease in the oligomer size from 40.7 S in crowding agents to 10.7 S in diluted solution has been reported [142]. In contrast, results for bovine αL at different concentrations reported only slight concentration dependent size changes between 5-10 nm in SAXS experiments [143], or an average diameter of 15 nm at concentrations up to 290 mg/mL [144].…”

Section: Structural Comparison Of αA and αBmentioning

confidence: 99%

Proteinaceous Transformers: Structural and Functional Variability of Human sHsps

Riedl¹,

Strauch²,

Catici³

et al. 2020

IJMS

View full text Add to dashboard Cite

The proteostasis network allows organisms to support and regulate the life cycle of proteins. Especially regarding stress, molecular chaperones represent the main players within this network. Small heat shock proteins (sHsps) are a diverse family of ATP-independent molecular chaperones acting as the first line of defense in many stress situations. Thereby, the promiscuous interaction of sHsps with substrate proteins results in complexes from which the substrates can be refolded by ATP-dependent chaperones. Particularly in vertebrates, sHsps are linked to a broad variety of diseases and are needed to maintain the refractive index of the eye lens. A striking key characteristic of sHsps is their existence in ensembles of oligomers with varying numbers of subunits. The respective dynamics of these molecules allow the exchange of subunits and the formation of hetero-oligomers. Additionally, these dynamics are closely linked to the chaperone activity of sHsps. In current models a shift in the equilibrium of the sHsp ensemble allows regulation of the chaperone activity, whereby smaller oligomers are commonly the more active species. Different triggers reversibly change the oligomer equilibrium and regulate the activity of sHsps. However, a finite availability of high-resolution structures of sHsps still limits a detailed mechanistic understanding of their dynamics and the correlating recognition of substrate proteins. Here we summarize recent advances in understanding the structural and functional relationships of human sHsps with a focus on the eye-lens αA- and αB-crystallins.

show abstract

Formation and physicochemical properties of glycogen phosphorylase in complex with a cationic polyelectrolyte

Neofytos

Papagiannopoulos

Chrysina

et al. 2022

International Journal of Biological Macromolecules

View full text Add to dashboard Cite

Oligomeric state of αB-crystallin under crowded conditions

Cited by 9 publications

References 34 publications

Chaperone-Like Activity of HSPB5: The Effects of Quaternary Structure Dynamics and Crowding

Chaperone-Like Activity of HSPB5: The Effects of Quaternary Structure Dynamics and Crowding

Proteinaceous Transformers: Structural and Functional Variability of Human sHsps

Formation and physicochemical properties of glycogen phosphorylase in complex with a cationic polyelectrolyte

Contact Info

Product

Resources

About