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Cooperation of Hsp70 and Hsp100 chaperone machines in protein disaggregation

Unicellular and sessile organisms are particularly exposed to environmental stress such as heat shock causing accumulation and aggregation of misfolded protein species. To counteract protein aggregation, bacteria, fungi, and plants encode a bi-chaperone system composed of ATP-dependent Hsp70 and hex...

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Autores principales: Mogk, Axel, Kummer, Eva, Bukau, Bernd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436881/
https://www.ncbi.nlm.nih.gov/pubmed/26042222
http://dx.doi.org/10.3389/fmolb.2015.00022
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author Mogk, Axel
Kummer, Eva
Bukau, Bernd
author_facet Mogk, Axel
Kummer, Eva
Bukau, Bernd
author_sort Mogk, Axel
collection PubMed
description Unicellular and sessile organisms are particularly exposed to environmental stress such as heat shock causing accumulation and aggregation of misfolded protein species. To counteract protein aggregation, bacteria, fungi, and plants encode a bi-chaperone system composed of ATP-dependent Hsp70 and hexameric Hsp100 (ClpB/Hsp104) chaperones, which rescue aggregated proteins and provide thermotolerance to cells. The partners act in a hierarchic manner with Hsp70 chaperones coating first the surface of protein aggregates and next recruiting Hsp100 through direct physical interaction. Hsp100 proteins bind to the ATPase domain of Hsp70 via their unique M-domain. This extra domain functions as a molecular toggle allosterically controlling ATPase and threading activities of Hsp100. Interactions between neighboring M-domains and the ATPase ring keep Hsp100 in a repressed state exhibiting low ATP turnover. Breakage of intermolecular M-domain interactions and dissociation of M-domains from the ATPase ring relieves repression and allows for Hsp70 interaction. Hsp70 binding in turn stabilizes Hsp100 in the activated state and primes Hsp100 ATPase domains for high activity upon substrate interaction. Hsp70 thereby couples Hsp100 substrate binding and motor activation. Hsp100 activation presumably relies on increased subunit cooperation leading to high ATP turnover and threading power. This Hsp70-mediated activity control of Hsp100 is crucial for cell viability as permanently activated Hsp100 variants are toxic. Hsp100 activation requires simultaneous binding of multiple Hsp70 partners, restricting high Hsp100 activity to the surface of protein aggregates and ensuring Hsp100 substrate specificity.
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spelling pubmed-44368812015-06-03 Cooperation of Hsp70 and Hsp100 chaperone machines in protein disaggregation Mogk, Axel Kummer, Eva Bukau, Bernd Front Mol Biosci Molecular Biosciences Unicellular and sessile organisms are particularly exposed to environmental stress such as heat shock causing accumulation and aggregation of misfolded protein species. To counteract protein aggregation, bacteria, fungi, and plants encode a bi-chaperone system composed of ATP-dependent Hsp70 and hexameric Hsp100 (ClpB/Hsp104) chaperones, which rescue aggregated proteins and provide thermotolerance to cells. The partners act in a hierarchic manner with Hsp70 chaperones coating first the surface of protein aggregates and next recruiting Hsp100 through direct physical interaction. Hsp100 proteins bind to the ATPase domain of Hsp70 via their unique M-domain. This extra domain functions as a molecular toggle allosterically controlling ATPase and threading activities of Hsp100. Interactions between neighboring M-domains and the ATPase ring keep Hsp100 in a repressed state exhibiting low ATP turnover. Breakage of intermolecular M-domain interactions and dissociation of M-domains from the ATPase ring relieves repression and allows for Hsp70 interaction. Hsp70 binding in turn stabilizes Hsp100 in the activated state and primes Hsp100 ATPase domains for high activity upon substrate interaction. Hsp70 thereby couples Hsp100 substrate binding and motor activation. Hsp100 activation presumably relies on increased subunit cooperation leading to high ATP turnover and threading power. This Hsp70-mediated activity control of Hsp100 is crucial for cell viability as permanently activated Hsp100 variants are toxic. Hsp100 activation requires simultaneous binding of multiple Hsp70 partners, restricting high Hsp100 activity to the surface of protein aggregates and ensuring Hsp100 substrate specificity. Frontiers Media S.A. 2015-05-19 /pmc/articles/PMC4436881/ /pubmed/26042222 http://dx.doi.org/10.3389/fmolb.2015.00022 Text en Copyright © 2015 Mogk, Kummer and Bukau. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Mogk, Axel
Kummer, Eva
Bukau, Bernd
Cooperation of Hsp70 and Hsp100 chaperone machines in protein disaggregation
title Cooperation of Hsp70 and Hsp100 chaperone machines in protein disaggregation
title_full Cooperation of Hsp70 and Hsp100 chaperone machines in protein disaggregation
title_fullStr Cooperation of Hsp70 and Hsp100 chaperone machines in protein disaggregation
title_full_unstemmed Cooperation of Hsp70 and Hsp100 chaperone machines in protein disaggregation
title_short Cooperation of Hsp70 and Hsp100 chaperone machines in protein disaggregation
title_sort cooperation of hsp70 and hsp100 chaperone machines in protein disaggregation
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436881/
https://www.ncbi.nlm.nih.gov/pubmed/26042222
http://dx.doi.org/10.3389/fmolb.2015.00022
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