The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70

AbstractIn human cells under stress conditions, misfolded polypeptides can form potentially cytotoxic insoluble aggregates. To eliminate aggregates, the HSP70 chaperone machinery extracts and resolubilizes polypeptides for triage to refolding or degradation. Yeast and bacterial chaperones of the small heat-shock protein (sHSP) family can bind substrates at early stages of misfolding, during the aggregation process. The co-aggregated sHSPs then facilitate downstream disaggregation by HSP70. Because it is unknown whether a human sHSP has this activity, we investigated the disaggregation role of human HSPB1. HSPB1 co-aggregated with unfolded protein substrates, firefly luciferase and mammalian lactate dehydrogenase. The co-aggregates formed with HSPB1 were smaller and more regularly shaped than those formed in its absence. Importantly, co-aggregation promoted the efficient disaggregation and refolding of the substrates, led by HSP70. HSPB1 itself was also extracted during disaggregation, and its homo-oligomerization ability was not required. Therefore, we propose that a human sHSP is an integral part of the chaperone network for protein disaggregation.

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Role of the Conserved SRLFDQFFG Region of α-Crystallin, a Small Heat Shock Protein

Journal of Biological Chemistry ◽

10.1074/jbc.m307523200 ◽

2003 ◽

Vol 278 (51) ◽

pp. 51159-51166 ◽

Cited By ~ 52

Author(s):

Saloni Yatin Pasta ◽

Bakthisaran Raman ◽

Tangirala Ramakrishna ◽

Ch. Mohan Rao

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Small Heat Shock Protein

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Role of Small Heat Shock Protein HspB5 in Cancer

Heat Shock Proteins - The Big Book on Small Heat Shock Proteins ◽

10.1007/978-3-319-16077-1_12 ◽

2015 ◽

pp. 301-314 ◽

Cited By ~ 1

Author(s):

Wilbert C. Boelens

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Small Heat Shock Protein

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THE IMPORTANCE OF HSP-25 IN CAENORHABDITIS ELEGANS LONGEVITY

Innovation in Aging ◽

10.1093/geroni/igz038.3176 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S865-S865

Author(s):

Niaya James ◽

Jessica L Scheirer ◽

Karl Rodriguez

Keyword(s):

Heat Stress ◽

Caenorhabditis Elegans ◽

Heat Shock ◽

Model Organism ◽

Small Heat Shock Protein ◽

Health Science ◽

Science Center ◽

Knock Out ◽

University Of Texas

Abstract Karl A. Rodriguez’s laboratory at the University of Texas Health Science Center, San Antonio, Texas, is interested in the role of small heat shock proteins in the proteostasis network and aging using the model organism, Caenorhabditis elegans. Molecular chaperones facilitate protein folding and improve the degradation activity of the proteasome and autolysosome hence decreasing disease-associated aggregates. Previous work in rodents have shown an increase in expression levels of the small heat shock protein 25 (HSP-25) correlates with maximum lifespan potential. To further explore the role of HSP-25 in C. elegans, two HSP-25 knock-out strains were exposed to a one-hour heat stress, heat shock, and two non-heat stress conditions.

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Protective role of Mycobacterium leprae small heat-shock protein in heterologous hosts, Escherichia coli and Mycobacterium smegmatis, grown under stress

Journal of Medical Microbiology ◽

10.1099/jmm.0.057851-0 ◽

2013 ◽

Vol 62 (7) ◽

pp. 959-967 ◽

Cited By ~ 9

Author(s):

Jayapal Jeya Maheshwari ◽

Kuppamuthu Dharmalingam

Keyword(s):

Escherichia Coli ◽

Heat Shock ◽

Heat Shock Protein ◽

Mycobacterium Smegmatis ◽

Small Heat Shock Protein ◽

Mycobacterium Leprae ◽

Protective Role ◽

Low Oxygen

The aim of this study is to examine the in vivo role of a small heat-shock protein (sHsp18) from Mycobacterium leprae in the survival of heterologous recombinant hosts carrying the gene encoding this protein under different environmental conditions that are normally encountered by M. leprae during its infection of the human host. Using an Escherichia coli system where shsp18 expression is controlled by its native promoter, we show that expression of shsp18 is induced under low oxygen tension, nutrient depletion and oxidative stress, all of which reflect the natural internal environment of the granulomas where the pathogen resides for long periods. We demonstrate the in vivo chaperone activity of sHsp18 through its ability to confer survival advantage to recombinant E. coli at heat-shock temperatures. Additional evidence for the protective role of sHsp18 was obtained when Mycobacterium smegmatis harbouring a copy of shsp18 was found to multiply better in human macrophages. Furthermore, the autokinase activity of sHsp18 protein demonstrated for what is believed to be the first time in this study implies that some of the functions of sHsp18 might be controlled by the phosphorylation state of this protein. Results from this study suggest that shsp18 might be one of the factors that facilitate the survival and persistence of M. leprae under stress and autophosphorylation of sHsp18 protein could be a mechanism used by this protein to sense changes in the external environment.

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Adaptation of the Wine Bacterium Oenococcus oeni to Ethanol Stress: Role of the Small Heat Shock Protein Lo18 in Membrane Integrity

Applied and Environmental Microbiology ◽

10.1128/aem.04178-13 ◽

2014 ◽

Vol 80 (10) ◽

pp. 2973-2980 ◽

Cited By ~ 33

Author(s):

Magali Maitre ◽

Stéphanie Weidmann ◽

Florence Dubois-Brissonnet ◽

Vanessa David ◽

Jacques Covès ◽

...

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Phospholipid Composition ◽

Small Heat Shock Protein ◽

Oenococcus Oeni ◽

Lipid Binding ◽

Phospholipid Content ◽

Ethanol Stress ◽

Content Type

ABSTRACTMalolactic fermentation in wine is often carried out byOenococcus oeni. Wine is a stressful environment for bacteria because ethanol is a toxic compound that impairs the integrity of bacterial membranes. The small heat shock protein (sHsp) Lo18 is an essential actor of the stress response inO. oeni. Lo18 prevents the thermal aggregation of proteins and plays a crucial role in membrane quality control. Here, we investigated the interaction between Lo18 and four types of liposomes: one was prepared fromO. oenigrown under optimal growth conditions (here, control liposomes), one was prepared fromO. oenigrown in the presence of 8% ethanol (here, ethanol liposomes), one was prepared from synthetic phospholipids, and one was prepared from phospholipids fromBacillus subtilisorLactococcus lactis. We observed the strongest interaction between Lo18 and control liposomes. The lipid binding activity of Lo18 required the dissociation of oligomeric structures into dimers. Protein protection experiments carried out in the presence of the liposomes fromO. oenisuggested that Lo18 had a higher affinity for control liposomes than for a model protein. In anisotropy experiments, we mimicked ethanol action by temperature-dependent fluidization of the liposomes. Results suggest that the principal determinant of Lo18-membrane interaction is lipid bilayer phase behavior rather than phospholipid composition. We suggest a model to describe the ethanol adaptation ofO. oeni. This model highlights the dual role of Lo18 in the protection of proteins from aggregation and membrane stabilization and suggests how modifications of phospholipid content may be a key factor determining the balance between these two functions.

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Small heat-shock protein Hsp12 contributes to yeast tolerance to freezing stress

Microbiology ◽

10.1099/mic.0.025981-0 ◽

2009 ◽

Vol 155 (6) ◽

pp. 2021-2028 ◽

Cited By ~ 29

Author(s):

A. Pacheco ◽

C. Pereira ◽

M. J. Almeida ◽

M. J. Sousa

Keyword(s):

Heat Shock ◽

Freezing Tolerance ◽

Small Heat Shock Protein ◽

Yeast Cells ◽

Freezing Stress ◽

Prolonged Storage ◽

Null Mutant ◽

Wild Type ◽

Shock Proteins

The HSP12 gene encodes one of the two major small heat-shock proteins of Saccharomyces cerevisiae and is induced under different conditions, such as low and high temperatures, osmotic or oxidative stress and high sugar or ethanol concentrations. However, few studies could demonstrate any correlation between HSP12 deletion or overexpression and a phenotype of sensitivity/resistance, making it difficult to attribute a role for Hsp12p under several of these stress conditions. We investigated the possible role of Hsp12p in yeast freezing tolerance. Contrary to what would be expected, the hsp12 null mutant when subjected to prolonged storage at −20 °C showed an increased resistance to freezing when compared with the isogenic wild-type strain. Because the mutant strain displayed a higher intracellular trehalose concentration than the wild-type, which could mask the effect of manipulating HSP12, we overexpressed the HSP12 gene in a trehalose-6-phosphate synthase (TPS1) null mutant. The tps1Δ strain overexpressing HSP12 showed an increase in resistance to freezing storage, indicating that Hsp12p plays a role in freezing tolerance in a way that seems to be interchangeable with trehalose. In addition, we show that overexpression of HSP12 in this tps1Δ strain also increased resistance to heat shock and that absence of HSP12 compromises the ability of yeast cells to accumulate high levels of trehalose in response to a mild heat stress.

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The Essential Role of the Flexible Termini in the Temperature-responsiveness of the Oligomeric State and Chaperone-like Activity for the Polydisperse Small Heat Shock Protein IbpB from Escherichia coli

Journal of Molecular Biology ◽

10.1016/j.jmb.2005.01.029 ◽

2005 ◽

Vol 347 (4) ◽

pp. 871-884 ◽

Cited By ~ 47

Author(s):

Wangwang Jiao ◽

Mengding Qian ◽

Pulin Li ◽

Lei Zhao ◽

Zengyi Chang

Keyword(s):

Escherichia Coli ◽

Heat Shock ◽

Heat Shock Protein ◽

Essential Role ◽

Small Heat Shock Protein ◽

Oligomeric State

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The cardioprotective role of small heat-shock protein 20

Biochemical Society Transactions ◽

10.1042/bst20130272 ◽

2014 ◽

Vol 42 (2) ◽

pp. 270-273 ◽

Cited By ~ 13

Author(s):

Tamara P. Martin ◽

Susan Currie ◽

George S. Baillie

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Therapeutic Agent ◽

Contractile Function ◽

Small Heat Shock Protein ◽

Dependent Protein Kinase ◽

Heat Shock Protein 20 ◽

Dependent Protein ◽

Stress Damage

The small HSP (heat-shock protein) HSP20 is a molecular chaperone that is transiently up-regulated in response to cellular stress/damage. Although ubiquitously expressed in various tissues, it is most highly expressed in skeletal, cardiac and smooth muscle. Phosphorylation at Ser16 by PKA (cAMP-dependent protein kinase) is essential for HSP20 to confer its protective qualities. HSP20 and its phosphorylation have been implicated in a variety of pathophysiological processes, but most prominently cardiovascular disease. A wealth of knowledge of the importance of HSP20 in contractile function and cardioprotection has been gained over the last decade. The present mini-review highlights more recent findings illustrating the cardioprotective properties of HSP20 and its potential as a therapeutic agent.

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