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De novo designed Hsp70 activator dissolves intracellular condensates
Protein quality control (PQC) is carried out in part by the chaperone Hsp70, in concert with adapters of the J-domain protein (JDP) family. The JDPs, also called Hsp40s, are thought to recruit Hsp70 into complexes with specific client proteins. However, the molecular principles regulating this proce...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541127/ https://www.ncbi.nlm.nih.gov/pubmed/37781598 http://dx.doi.org/10.1101/2023.09.18.558356 |
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author | Zhang, Jason Z Greenwood, Nathan Hernandez, Jason Cuperus, Josh T Huang, Buwei Ryder, Bryan D Queitsch, Christine Gestwicki, Jason E Baker, David |
author_facet | Zhang, Jason Z Greenwood, Nathan Hernandez, Jason Cuperus, Josh T Huang, Buwei Ryder, Bryan D Queitsch, Christine Gestwicki, Jason E Baker, David |
author_sort | Zhang, Jason Z |
collection | PubMed |
description | Protein quality control (PQC) is carried out in part by the chaperone Hsp70, in concert with adapters of the J-domain protein (JDP) family. The JDPs, also called Hsp40s, are thought to recruit Hsp70 into complexes with specific client proteins. However, the molecular principles regulating this process are not well understood. We describe the de novo design of a set of Hsp70 binding proteins that either inhibited or stimulated Hsp70’s ATPase activity; a stimulating design promoted the refolding of denatured luciferase in vitro, similar to native JDPs. Targeting of this design to intracellular condensates resulted in their nearly complete dissolution. The designs inform our understanding of chaperone structure-function relationships and provide a general and modular way to target PQC systems to condensates and other cellular targets. |
format | Online Article Text |
id | pubmed-10541127 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-105411272023-10-01 De novo designed Hsp70 activator dissolves intracellular condensates Zhang, Jason Z Greenwood, Nathan Hernandez, Jason Cuperus, Josh T Huang, Buwei Ryder, Bryan D Queitsch, Christine Gestwicki, Jason E Baker, David bioRxiv Article Protein quality control (PQC) is carried out in part by the chaperone Hsp70, in concert with adapters of the J-domain protein (JDP) family. The JDPs, also called Hsp40s, are thought to recruit Hsp70 into complexes with specific client proteins. However, the molecular principles regulating this process are not well understood. We describe the de novo design of a set of Hsp70 binding proteins that either inhibited or stimulated Hsp70’s ATPase activity; a stimulating design promoted the refolding of denatured luciferase in vitro, similar to native JDPs. Targeting of this design to intracellular condensates resulted in their nearly complete dissolution. The designs inform our understanding of chaperone structure-function relationships and provide a general and modular way to target PQC systems to condensates and other cellular targets. Cold Spring Harbor Laboratory 2023-09-19 /pmc/articles/PMC10541127/ /pubmed/37781598 http://dx.doi.org/10.1101/2023.09.18.558356 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Zhang, Jason Z Greenwood, Nathan Hernandez, Jason Cuperus, Josh T Huang, Buwei Ryder, Bryan D Queitsch, Christine Gestwicki, Jason E Baker, David De novo designed Hsp70 activator dissolves intracellular condensates |
title | De novo designed Hsp70 activator dissolves intracellular condensates |
title_full | De novo designed Hsp70 activator dissolves intracellular condensates |
title_fullStr | De novo designed Hsp70 activator dissolves intracellular condensates |
title_full_unstemmed | De novo designed Hsp70 activator dissolves intracellular condensates |
title_short | De novo designed Hsp70 activator dissolves intracellular condensates |
title_sort | de novo designed hsp70 activator dissolves intracellular condensates |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541127/ https://www.ncbi.nlm.nih.gov/pubmed/37781598 http://dx.doi.org/10.1101/2023.09.18.558356 |
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