Cargando…

Metazoan Hsp70-based protein disaggregases: emergence and mechanisms

Proteotoxic stresses and aging cause breakdown of cellular protein homeostasis, allowing misfolded proteins to form aggregates, which dedicated molecular machines have evolved to solubilize. In bacteria, fungi, protozoa and plants protein disaggregation involves an Hsp70•J-protein chaperone system,...

Descripción completa

Detalles Bibliográficos
Autores principales: Nillegoda, Nadinath B., 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/PMC4598581/
https://www.ncbi.nlm.nih.gov/pubmed/26501065
http://dx.doi.org/10.3389/fmolb.2015.00057
_version_ 1782394092159762432
author Nillegoda, Nadinath B.
Bukau, Bernd
author_facet Nillegoda, Nadinath B.
Bukau, Bernd
author_sort Nillegoda, Nadinath B.
collection PubMed
description Proteotoxic stresses and aging cause breakdown of cellular protein homeostasis, allowing misfolded proteins to form aggregates, which dedicated molecular machines have evolved to solubilize. In bacteria, fungi, protozoa and plants protein disaggregation involves an Hsp70•J-protein chaperone system, which loads and activates a powerful AAA+ ATPase (Hsp100) disaggregase onto protein aggregate substrates. Metazoans lack cytosolic and nuclear Hsp100 disaggregases but still eliminate protein aggregates. This longstanding puzzle of protein quality control is now resolved. Robust protein disaggregation activity recently shown for the metazoan Hsp70-based disaggregases relies instead on a crucial cooperation between two J-protein classes and interaction with the Hsp110 co-chaperone. An expanding multiplicity of Hsp70 and J-protein family members in metazoan cells facilitates different configurations of this Hsp70-based disaggregase allowing unprecedented versatility and specificity in protein disaggregation. Here we review the architecture, operation, and adaptability of the emerging metazoan disaggregation system and discuss how this evolved.
format Online
Article
Text
id pubmed-4598581
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-45985812015-10-23 Metazoan Hsp70-based protein disaggregases: emergence and mechanisms Nillegoda, Nadinath B. Bukau, Bernd Front Mol Biosci Molecular Biosciences Proteotoxic stresses and aging cause breakdown of cellular protein homeostasis, allowing misfolded proteins to form aggregates, which dedicated molecular machines have evolved to solubilize. In bacteria, fungi, protozoa and plants protein disaggregation involves an Hsp70•J-protein chaperone system, which loads and activates a powerful AAA+ ATPase (Hsp100) disaggregase onto protein aggregate substrates. Metazoans lack cytosolic and nuclear Hsp100 disaggregases but still eliminate protein aggregates. This longstanding puzzle of protein quality control is now resolved. Robust protein disaggregation activity recently shown for the metazoan Hsp70-based disaggregases relies instead on a crucial cooperation between two J-protein classes and interaction with the Hsp110 co-chaperone. An expanding multiplicity of Hsp70 and J-protein family members in metazoan cells facilitates different configurations of this Hsp70-based disaggregase allowing unprecedented versatility and specificity in protein disaggregation. Here we review the architecture, operation, and adaptability of the emerging metazoan disaggregation system and discuss how this evolved. Frontiers Media S.A. 2015-10-09 /pmc/articles/PMC4598581/ /pubmed/26501065 http://dx.doi.org/10.3389/fmolb.2015.00057 Text en Copyright © 2015 Nillegoda 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
Nillegoda, Nadinath B.
Bukau, Bernd
Metazoan Hsp70-based protein disaggregases: emergence and mechanisms
title Metazoan Hsp70-based protein disaggregases: emergence and mechanisms
title_full Metazoan Hsp70-based protein disaggregases: emergence and mechanisms
title_fullStr Metazoan Hsp70-based protein disaggregases: emergence and mechanisms
title_full_unstemmed Metazoan Hsp70-based protein disaggregases: emergence and mechanisms
title_short Metazoan Hsp70-based protein disaggregases: emergence and mechanisms
title_sort metazoan hsp70-based protein disaggregases: emergence and mechanisms
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598581/
https://www.ncbi.nlm.nih.gov/pubmed/26501065
http://dx.doi.org/10.3389/fmolb.2015.00057
work_keys_str_mv AT nillegodanadinathb metazoanhsp70basedproteindisaggregasesemergenceandmechanisms
AT bukaubernd metazoanhsp70basedproteindisaggregasesemergenceandmechanisms