Structural and Functional Aspects of Hetero-oligomers Formed by the Small Heat Shock Proteins αB-Crystallin and HSP27

Aquilina, J. Andrew; Shrestha, Sudichhya; Morris, Amie M.; Ecroyd, Heath

doi:10.1074/jbc.m112.443812

Cited by 72 publications

(65 citation statements)

References 47 publications

(45 reference statements)

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“…However, this oligomer consists of both the cleaved and uncleaved proteins. It is thus likely that the two different forms of the protein cross oligomerize to form a hetero-oligomer, a phenomenon observed previously in sHSP mixtures (Studer and Narberhaus, 2000;Aquilina et al 2013). The difference in hydrodynamic radii between the homo-and hetero-oligomeric forms (5.3 and 4 nm, respectively) suggests that the oligomeric assemblies are different.…”

Section: Hsp24 Mitochondriamentioning

confidence: 80%

Characterization of rice small heat shock proteins targeted to different cellular organelles

Mani

Ramakrishna

Suguna

2015

Cell Stress and Chaperones

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Small heat shock proteins (sHSPs) are a family of ATP-independent molecular chaperones which prevent cellular protein aggregation by binding to misfolded proteins. sHSPs form large oligomers that undergo drastic rearrangement/dissociation in order to execute their chaperone activity in protecting substrates from stress. Substrate-binding sites on sHSPs have been predominantly mapped on their intrinsically disordered N-terminal arms. This region is highly variable in sequence and length across species, and has been implicated in both oligomer formation and in mediating chaperone activity. Here, we present our results on the functional and structural characterization of five sHSPs in rice, each differing in their subcellular localisation, viz., cytoplasm, nucleus, chloroplast, mitochondria and peroxisome. We performed activity assays and dynamic light scattering studies to highlight differences in the chaperone activity and quaternary assembly of sHSPs targeted to various organelles. By cloning constructs that differ in the length and sequence of the tag in the N-terminal region, we have probed the sensitivity of sHSP oligomer assembly and chaperone activity to the length and amino acid composition of the N-terminus. In particular, we have shown that the incorporation of an N-terminal tag has significant consequences on sHSP quaternary structure.

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Section: Hsp24 Mitochondriamentioning

confidence: 80%

Characterization of rice small heat shock proteins targeted to different cellular organelles

Mani

Ramakrishna

Suguna

2015

Cell Stress and Chaperones

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“…Classically this includes the -crystallins of the eye lens, but numerous other vertebrate sHSPs have been indicated as coassembling [6,11]. Typically the interaction between two or more sHSPs appears to be stochastic in nature, where the representation of each component in the mixed oligomer purely reflects their input concentration [14,22]. However, a number of vertebrate sHSPs have been shown to form heterooligomers that contain a fixed ratio of the component protomers, independent of the starting proportions used [16,23].…”

Section: Discussionmentioning

confidence: 99%

“…Alone these two sHSPs are found as distinctly different assemblies. HSPB1 forms large oligomers, typically observed amongst representatives of this family of chaperones, while HSPB6 only forms dimers in solution [14,[20][21][22]. Previous studies of the heterooligomers formed between recombinant HSPB1 and HSPB6 have shown that they are considerably more polydisperse in size than the component sHSPs, with a molecular weight that spans the range between the two individual proteins [21].…”

Section: Introductionmentioning

confidence: 99%

The preferential heterodimerization of human small heat shock proteins HSPB1 and HSPB6 is dictated by the N-terminal domain

Heirbaut

Lermyte

Martin

et al. 2016

Archives of Biochemistry and Biophysics

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Small heat shock proteins are ATP-independent molecular chaperones. Their function is to bind partially unfolded proteins under stress conditions. In vivo, members of this chaperone family are known to preferentially assemble together forming large, polydisperse heterooligomers. The exact molecular mechanisms that drive specific heteroassociation are currently unknown. Here we study the oligomers formed between human HSPB1 and HSPB6.Using small-angle X-ray scattering we could characterize two distinct heterooligomeric species present in solution. By employing native mass spectrometry we show that such assemblies are formed purely from heterodimeric building blocks, in line with earlier crosslinking studies. Crucially, a detailed analysis of truncation variants reveals that the preferential association between these two sHSPs is solely mediated by their disordered Nterminal domains.

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“…and Bc [81,83]. The hetero-oligomers had masses and thermo-stabilities intermediate of the homo-oligomers and their chaperone ability was equivalent to that of αBc (and better than Hsp27).…”

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confidence: 99%

Small heat-shock proteins: important players in regulating cellular proteostasis

Treweek

Meehan

Ecroyd

et al. 2014

Cell. Mol. Life Sci.

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180

177

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Small heat-shock proteins (sHsps) are a diverse family of intra-cellular molecular chaperone proteins that play a critical role in mitigating and preventing protein aggregation under stress conditions such as elevated temperature, oxidation and infection. In doing so, they assist in the maintenance of protein homeostasis (proteostasis) thereby avoiding the deleterious effects that result from loss of protein function and/or protein aggregation. The chaperone properties of sHsps are therefore employed extensively in many tissues to prevent the development of diseases associated with protein aggregation. Significant progress has been made of late in understanding the structure and chaperone mechanism of sHsps. In this review, we discuss some of these advances, with a focus on mammalian sHsp hetero-oligomerisation, the mechanism by which sHsps act as molecular chaperones to prevent both amorphous and fibrillar protein aggregation, and the role of posttranslational modifications in sHsp chaperone function, particularly in the context of disease. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 Abstract (word count = 159)Small heat-shock proteins (sHsps) are a diverse family of intracellular molecular chaperone proteins that play a critical role in preventing protein unfolding, misfolding and aggregation, particularly under stress conditions such as elevated temperature, oxidation and infection. In doing so, they assist in the maintenance of protein homeostasis (proteostasis) and thereby avoid the deleterious effects that result from loss of protein function and/or protein aggregation. The chaperone properties of sHsps are therefore employed extensively in many tissues to prevent the development of diseases associated with protein aggregation. There has been much research into the structure and mechanism of chaperone action of sHsps over approximately the past 30 years, and significant progress has been made of late, however, there are still many unanswered questions relating to these aspects of sHsps. In this review, we outline some of the recent advances in understanding the structure and function of mammalian sHsps, particularly in the context of their many and varied roles in disease.

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Structural and Functional Aspects of Hetero-oligomers Formed by the Small Heat Shock Proteins αB-Crystallin and HSP27

Cited by 72 publications

References 47 publications

Characterization of rice small heat shock proteins targeted to different cellular organelles

Characterization of rice small heat shock proteins targeted to different cellular organelles

The preferential heterodimerization of human small heat shock proteins HSPB1 and HSPB6 is dictated by the N-terminal domain

Small heat-shock proteins: important players in regulating cellular proteostasis

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