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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...

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Autores principales: Carroni, Marta, Franke, Kamila B, Maurer, Michael, Jäger, Jasmin, Hantke, Ingo, Gloge, Felix, Linder, Daniela, Gremer, Sebastian, Turgay, Kürşad, Bukau, Bernd, Mogk, Axel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
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.
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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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