Small heat shock protein Hsp27 protects myosin S1 from heat‐induced aggregation, but not from thermal denaturation and ATPase inactivation

Markov, Denis I.; Pivovarova, Anastasia V.; Chernik, Ivan S.; Gusev, Nikolai B.; Levitsky, Dmitrii I.

doi:10.1016/j.febslet.2008.03.035

Cited by 29 publications

(26 citation statements)

References 29 publications

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“…Thus, posttranslational modifications of the N-terminal domain can significantly affect the quaternary structure of the small heat shock proteins. Phosphorylation affects the chaperone-like activity of Hsp27 and its orthologs, however the amplitude and the sign of this effect seem to depend on experimental conditions and on the nature of model target proteins used in experiment [77,85,86,88,89].…”

Section: N-terminal Domain Of Small Heat Shock Proteinsmentioning

confidence: 94%

The Role of Intrinsically Disordered Regions in the Structure and Functioning of Small Heat Shock Proteins

Sudnitsyna¹,

Mymrikov²,

Seit-Nebi³

et al. 2012

CPPS

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Small heat shock proteins (sHsp) form a large ubiquitous family of proteins expressed in all phyla of living organisms. The members of this family have low molecular masses (13-43 kDa) and contain a conservative α-crystallin domain. This domain (about 90 residues) consists of several β-strands forming two β-sheets packed in immunoglobulinlike manner. The α-crystallin domain plays an important role in formation of stable sHsp dimers, which are the building blocks of the large sHsp oligomers. A large N-terminal domain and a short C-terminal extension flank the α-crystallin domain. Both the N-terminal domain and the C-terminal extension are flexible, susceptible to proteolysis, prone to posttranslational modifications, and are predominantly intrinsically disordered. Differently oriented N-terminal domains interact with each other, with the core α-crystallin domain of the same or neighboring dimers and play important role in formation of large sHsp oligomers. Phosphorylation of certain sites in the N-terminal domain affects the sHsp quaternary structure, the sHsp interaction with target proteins and the sHsp chaperone-like activity. The C-terminal extension often carrying the conservative tripeptide (I/V/L)-X-(I/V/L) is capable of binding to a hydrophobic groove on the surface of the core α-crystallin domain of neighboring dimer, thus affecting the plasticity and the overall structure of sHsp oligomers. The Cterminal extension interacts with target proteins and affects their interaction with the α-crystallin domain increasing solubility of the complexes formed by sHsp and their targets. Thus, disordered N- and C-terminal sequences play important role in the structure, regulation and functioning of sHsp.

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Section: N-terminal Domain Of Small Heat Shock Proteinsmentioning

confidence: 94%

The Role of Intrinsically Disordered Regions in the Structure and Functioning of Small Heat Shock Proteins

Sudnitsyna¹,

Mymrikov²,

Seit-Nebi³

et al. 2012

CPPS

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“…Some in vitro studies concluded that the unphosphorylated oligomeric Hsp27 (or the murine isoform Hsp25) protects proteins against aggregation better than does the phosphorylation mimic (13,19,27), whereas others found no difference (16,28,29), and still other studies found that the mimic protects better than does the unphosphorylated wild type (27,30,31). In-cell studies found that phosphorylation of Hsp27 was essential for thermo-protection of actin filaments (32), and the Hsp27 phosphorylation mimic decreased inclusion body formation better than did unphosphorylated Hsp27 (33).…”

mentioning

confidence: 99%

Phosphorylation Dependence of Hsp27 Multimeric Size and Molecular Chaperone Function

Hayes

Napoli

Mazurkie

et al. 2009

Journal of Biological Chemistry

122

106

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The molecular chaperone Hsp27 exists as a distribution of large oligomers that are disassembled by phosphorylation at Ser-15, -78, and -82. It is controversial whether the unphosphorylated Hsp27 or the widely used triple Ser-to-Asp phosphomimic mutant is the more active molecular chaperone in vitro. This question was investigated here by correlating chaperone activity, as measured by the aggregation of reduced insulin or ␣-lactalbumin, with Hsp27 self-association as monitored by analytical ultracentrifugation. Furthermore, because the phospho-mimic is generally assumed to reproduce the phosphorylated molecule, the size and chaperone activity of phosphorylated Hsp27 were compared with that of the phospho-mimic. Hsp27 was triply phosphorylated by MAPKAP-2 kinase, and phosphorylation was tracked by urea-PAGE. An increasing degree of suppression of insulin or ␣-lactalbumin aggregation correlated with a decreasing Hsp27 self-association, which was the least for phosphorylated Hsp27 followed by the mimic followed by the unphosphorylated protein. It was also found that Hsp27 added to pre-aggregated insulin did not reverse aggregation but did inhibit these aggregates from assembling into even larger aggregates. This chaperone activity appears to be independent of Hsp27 phosphorylation. In conclusion, the most active chaperone of insulin and ␣-lactalbumin was the Hsp27 (elongated) dimer, the smallest Hsp27 subunit observed under physiological conditions. Next, the Hsp27 phospho-mimic is only a partial mimic of phosphorylated Hsp27, both in self-association and in chaperone function. Finally, the efficient inhibition of insulin aggregation by Hsp27 dimer led to the proposal of two models for this chaperone activity.

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“…In this respect, Hsp22 is quite different from all other mammalian sHsp studied by DSC, e.g. Hsp27 and α-crystallin, which demonstrated cooperative thermal transitions at~70°C for Hsp27 [25,33,34] and at 60°C for α-crystallin [35,36]. This indicates that Hsp22, in contrast with Hsp27 and α-crystallin, lacks rigid tertiary structure.…”

Section: Discussionmentioning

confidence: 69%

“…For instance, Hsp27-3D that unfolds at temperature higher than 70°C [25,33,34] is the most effective, whereas the wild type Hsp22 and especially its K141E mutant undergoing thermal unfolding at about 58 and 51°C are less effective in retarding F-actin aggregation that starts at about 55°C (Fig. 6).…”

Section: Effect Of Hsp22 and Its K141e Mutant On Heat-induced Aggregamentioning

confidence: 94%

Thermally induced structural changes of intrinsically disordered small heat shock protein Hsp22

Kazakov

Markov

Gusev

et al. 2009

Biophysical Chemistry

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Small heat shock protein Hsp27 protects myosin S1 from heat‐induced aggregation, but not from thermal denaturation and ATPase inactivation

Cited by 29 publications

References 29 publications

The Role of Intrinsically Disordered Regions in the Structure and Functioning of Small Heat Shock Proteins

The Role of Intrinsically Disordered Regions in the Structure and Functioning of Small Heat Shock Proteins

Phosphorylation Dependence of Hsp27 Multimeric Size and Molecular Chaperone Function

Thermally induced structural changes of intrinsically disordered small heat shock protein Hsp22

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