The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70

Abstract In 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 sm...

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Autores principales:	Conrado C. Gonçalves, Itai Sharon, T. Martin Schmeing, Carlos H. I. Ramos, Jason C. Young
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/da3504a65e704da49d5323a9fb4e6586
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spelling	oai:doaj.org-article:da3504a65e704da49d5323a9fb4e65862021-12-02T16:35:06ZThe chaperone HSPB1 prepares protein aggregates for resolubilization by HSP7010.1038/s41598-021-96518-x2045-2322https://doaj.org/article/da3504a65e704da49d5323a9fb4e65862021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96518-xhttps://doaj.org/toc/2045-2322Abstract In 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.Conrado C. GonçalvesItai SharonT. Martin SchmeingCarlos H. I. RamosJason C. YoungNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Conrado C. Gonçalves Itai Sharon T. Martin Schmeing Carlos H. I. Ramos Jason C. Young The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70
description	Abstract In 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.
format	article
author	Conrado C. Gonçalves Itai Sharon T. Martin Schmeing Carlos H. I. Ramos Jason C. Young
author_facet	Conrado C. Gonçalves Itai Sharon T. Martin Schmeing Carlos H. I. Ramos Jason C. Young
author_sort	Conrado C. Gonçalves
title	The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70
title_short	The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70
title_full	The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70
title_fullStr	The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70
title_full_unstemmed	The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70
title_sort	chaperone hspb1 prepares protein aggregates for resolubilization by hsp70
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/da3504a65e704da49d5323a9fb4e6586
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The chaperone HSPB1 prepares protein aggregates for resolubilization by HSP70

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