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Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control
Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essentia...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699869/ https://www.ncbi.nlm.nih.gov/pubmed/29165246 http://dx.doi.org/10.7554/eLife.30120 |
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author | Carroni, Marta Franke, Kamila B Maurer, Michael Jäger, Jasmin Hantke, Ingo Gloge, Felix Linder, Daniela Gremer, Sebastian Turgay, Kürşad Bukau, Bernd Mogk, Axel |
author_facet | Carroni, Marta Franke, Kamila B Maurer, Michael Jäger, Jasmin Hantke, Ingo Gloge, Felix Linder, Daniela Gremer, Sebastian Turgay, Kürşad Bukau, Bernd Mogk, Axel |
author_sort | Carroni, Marta |
collection | PubMed |
description | Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity. |
format | Online Article Text |
id | pubmed-5699869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-56998692017-11-24 Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control Carroni, Marta Franke, Kamila B Maurer, Michael Jäger, Jasmin Hantke, Ingo Gloge, Felix Linder, Daniela Gremer, Sebastian Turgay, Kürşad Bukau, Bernd Mogk, Axel eLife Biochemistry and Chemical Biology Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity. eLife Sciences Publications, Ltd 2017-11-22 /pmc/articles/PMC5699869/ /pubmed/29165246 http://dx.doi.org/10.7554/eLife.30120 Text en © 2017, Carroni et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Carroni, Marta Franke, Kamila B Maurer, Michael Jäger, Jasmin Hantke, Ingo Gloge, Felix Linder, Daniela Gremer, Sebastian Turgay, Kürşad Bukau, Bernd Mogk, Axel Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control |
title | Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control |
title_full | Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control |
title_fullStr | Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control |
title_full_unstemmed | Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control |
title_short | Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control |
title_sort | regulatory coiled-coil domains promote head-to-head assemblies of aaa+ chaperones essential for tunable activity control |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699869/ https://www.ncbi.nlm.nih.gov/pubmed/29165246 http://dx.doi.org/10.7554/eLife.30120 |
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