Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control

authored by

Marta Carroni, Kamila B. Franke, Michael Maurer, Jasmin Jäger, Ingo Hantke, Felix Gloge, Daniela Linder, Sebastian Gremer, Kürşad Turgay, Bernd Bukau, Axel Mogk

Abstract

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.

Organisation(s)

Institute of Microbiology

External Organisation(s)

Stockholm University
Heidelberg University
Wyatt Technology Europe

Type

Article

Journal

ELIFE

Volume

6

ISSN

2050-084X

Publication date

22.11.2017

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Neuroscience(all), Immunology and Microbiology(all), Biochemistry, Genetics and Molecular Biology(all)

Electronic version(s)

https://doi.org/10.7554/eLife.30120 (Access: Open)