Hsp104 and ClpB: protein disaggregating machines

Doyle, Shannon M.; Wickner, Sue

doi:10.1016/j.tibs.2008.09.010

Cited by 252 publications

(237 citation statements)

References 81 publications

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“…It is required at elevated temperatures, conferring compartment-specific thermotolerance to mitochondria and is necessary for the resolubilization of aggregated proteins in vivo (Schmitt et al 1996;Doyle and Wickner 2009). Hsp78 also functions in collaboration with proteolytic enzymes to facilitate protein turnover (Schmitt et al 1995;Voos 2009).…”

Section: Mitochondrial Quality Controlmentioning

confidence: 99%

Quality Control of Mitochondrial Proteostasis

Baker

Tatsuta²,

Langer

2011

Cold Spring Harbor Perspectives in Biology

223

193

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A decline in mitochondrial activity has been associated with aging and is a hallmark of many neurological diseases. Surveillance mechanisms acting at the molecular, organellar, and cellular level monitor mitochondrial integrity and ensure the maintenance of mitochondrial proteostasis. Here we will review the central role of mitochondrial chaperones and proteases, the cytosolic ubiquitin-proteasome system, and the mitochondrial unfolded response in this interconnected quality control network, highlighting the dual function of some proteases in protein quality control within the organelle and for the regulation of mitochondrial fusion and mitophagy.

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Section: Mitochondrial Quality Controlmentioning

confidence: 99%

Quality Control of Mitochondrial Proteostasis

Baker

Tatsuta²,

Langer

2011

Cold Spring Harbor Perspectives in Biology

223

193

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“…HSP101 is a molecular chaperone belonging to the ClpB/HSP100 family of AAA+ proteins (Lee et al, 2007;Doyle and Wickner, 2009). HSP104, the yeast (Saccharomyces cerevisiae) counterpart of HSP101, was shown to resolubilize heat-denatured proteins from insoluble aggregates (Parsell et al, 1994;Glover and Lindquist, 1998) and confer thermotolerance (Sanchez and Lindquist, 1990).…”

mentioning

confidence: 99%

Interplay between Heat Shock Proteins HSP101 and HSA32 Prolongs Heat Acclimation Memory Posttranscriptionally in Arabidopsis

Juan

Hsu

et al. 2013

Plant Physiology

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Heat acclimation improves the tolerance of organisms to severe heat stress. Our previous work showed that in Arabidopsis (Arabidopsis thaliana), the "memory" of heat acclimation treatment decayed faster in the absence of the heat-stress-associated 32-kD protein HSA32, a heat-induced protein predominantly found in plants. The HSA32 null mutant attains normal short-term acquired thermotolerance but is defective in long-term acquired thermotolerance. To further explore this phenomenon, we isolated Arabidopsis defective in long-term acquired thermotolerance (dlt) mutants using a forward genetic screen. Two recessive missense alleles, dlt1-1 and dlt1-2, encode the molecular chaperone heat shock protein101 (HSP101). Results of immunoblot analyses suggest that HSP101 enhances the translation of HSA32 during recovery after heat treatment, and in turn, HSA32 retards the decay of HSP101. The dlt1-1 mutation has little effect on HSP101 chaperone activity and thermotolerance function but compromises the regulation of HSA32. In contrast, dlt1-2 impairs the chaperone activity and thermotolerance function of HSP101 but not the regulation of HSA32. These results suggest that HSP101 has a dual function, which could be decoupled by the mutations. Pulse-chase analysis showed that HSP101 degraded faster in the absence of HSA32. The autophagic proteolysis inhibitor E-64d, but not the proteasome inhibitor MG132, inhibited the degradation of HSP101. Ectopic expression of HSA32 confirmed its effect on the decay of HSP101 at the posttranscriptional level and showed that HSA32 was not sufficient to confer long-term acquired thermotolerance when the HSP101 level was low. Taken together, we propose that a positive feedback loop between HSP101 and HSA32 at the protein level is a novel mechanism for prolonging the memory of heat acclimation.

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“…B acterial ClpB and yeast Hsp104 are ATP-dependent protein remodeling machines that function to disaggregate protein aggregates and reactivate proteins after extreme stress conditions (1)(2)(3). In the cell, ClpB acts in conjunction with the DnaK chaperone system and Hsp104 acts with the Hsp70 chaperone system (4,5).…”

mentioning

confidence: 99%

Coupling ATP utilization to protein remodeling by ClpB, a hexameric AAA+ protein

Hoskins

Doyle

Wickner

2009

Proc. Natl. Acad. Sci. U.S.A.

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ClpB and Hsp104 are members of the AAA؉ (ATPases associated with various cellular activities) family of proteins and are molecular machines involved in thermotolerance. They are hexameric proteins containing 12 ATP binding sites with two sites per protomer. ClpB and Hsp104 possess some innate protein remodeling activities; however, they require the collaboration of the DnaK/Hsp70 chaperone system to disaggregate and reactivate insoluble aggregated proteins. We investigated the mechanism by which ClpB couples ATP utilization to protein remodeling with and without the DnaK system. When wild-type ClpB, which is unable to remodel proteins alone in the presence of ATP, was mixed with a ClpB mutant that is unable to hydrolyze ATP, the heterohexamers surprisingly gained protein remodeling activity. Optimal protein remodeling by the heterohexamers in the absence of the DnaK system required approximately three active and three inactive protomers. In addition, the location of the active and inactive ATP binding sites in the hexamer was not important. The results suggest that in the absence of the DnaK system, ClpB acts by a probabilistic mechanism. However, when we measured protein disaggregation by ClpB heterohexamers in conjunction with the DnaK system, incorporation of a single inactive ClpB subunit blocked activity, supporting a sequential mechanism of ATP utilization. Taken together, the results suggest that the mechanism of ATP utilization by ClpB is adaptable and can vary depending on the specific substrate and the presence of the DnaK system.B acterial ClpB and yeast Hsp104 are ATP-dependent protein remodeling machines that function to disaggregate protein aggregates and reactivate proteins after extreme stress conditions (1-3). In the cell, ClpB acts in conjunction with the DnaK chaperone system and Hsp104 acts with the Hsp70 chaperone system (4, 5). DnaK and Hsp70 are members of another large, ubiquitous family of ATP-dependent molecular chaperones that mediate protein reactivation and remodeling in concert with two cochaperones, DnaJ and GrpE in prokaryotes and Hsp40 and NEF in eukaryotes (6). Alone, neither the DnaK/Hsp70 chaperone system nor ClpB/Hsp104 has the ability to reactivate large insoluble aggregates.ClpB/Hsp104 exists as a hexameric ring with an axial channel (7-10). Each protomer contains two AAAϩ (ATPases associated with various cellular activities) nucleotide-binding domains separated by a hinge region and preceded by an N-terminal domain (1, 7). The two AAAϩ domains contain characteristic motifs, including Walker A and B and sensor-1 and -2 motifs, as well as an arginine finger (11,12). Situated in the first AAAϩ domain is a long coiled-coil region, referred to as the middle domain, which is unique to ClpB, Hsp104, and their homologs.In vitro ClpB/Hsp104 solubilizes and reactivates protein aggregates in ATP-dependent reactions in collaboration with the DnaK/Hsp70 chaperone system (1-3). Although the roles of the two chaperone systems in disaggregation are not fully understood, it is likely that ...

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Hsp104 and ClpB: protein disaggregating machines

Cited by 252 publications

References 81 publications

Quality Control of Mitochondrial Proteostasis

Quality Control of Mitochondrial Proteostasis

Interplay between Heat Shock Proteins HSP101 and HSA32 Prolongs Heat Acclimation Memory Posttranscriptionally in Arabidopsis

Coupling ATP utilization to protein remodeling by ClpB, a hexameric AAA+ protein

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