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Structure of the central Staphylococcus aureus AAA+ protease MecA/ClpC/ClpP

Bacterial AAA+ proteases are composed of a AAA+ partner (e.g., ClpC) and an associated peptidase (e.g., ClpP). They represent ATP-fuelled and self-compartmentalized proteolytic machines that are crucial for stress resistance and virulence. ClpC requires cooperation with adaptor proteins such as MecA...

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Main Authors: Azinas, Stavros (Author) , Wallden, Karin (Author) , Katikaridis, Panagiotis (Author) , Jenne, Timo (Author) , Schahl, Adrien (Author) , Mogk, Axel (Author) , Carroni, Marta (Author)
Format: Article (Journal)
Language:English
Published: 14 October 2025
In: Communications biology
Year: 2025, Volume: 8, Pages: 1-18
ISSN:2399-3642
DOI:10.1038/s42003-025-08908-w
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s42003-025-08908-w
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s42003-025-08908-w
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Author Notes:Stavros Azinas, Karin Wallden, Panagiotis Katikaridis, Timo Jenne, Adrien Schahl, Axel Mogk & Marta Carroni
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Summary:Bacterial AAA+ proteases are composed of a AAA+ partner (e.g., ClpC) and an associated peptidase (e.g., ClpP). They represent ATP-fuelled and self-compartmentalized proteolytic machines that are crucial for stress resistance and virulence. ClpC requires cooperation with adaptor proteins such as MecA for activation and complex formation with ClpP. Here, we present the cryo-EM structure of the MecA/ClpC/ClpP complex from the major pathogen Staphylococcus aureus. MecA forms a dynamic crown on top of the ClpC/ClpP complex with its substrate-binding domain positioned near the ClpC pore site, likely facilitating substrate transfer. ClpC/ClpP complex formation involves ClpC P-loops and ClpP N-terminal β-hairpins, which insert into the central ClpC threading channel and contact sites next to the ClpC ATPase center. ClpC and ClpP interactions are asymmetric and dictated by the activity states of ClpC ATPase subunits. ClpP binding increases ClpC ATPase and threading activities in a β-hairpin dependent manner, illuminating an allosteric pathway in the cooperation of ATPase and peptidase components in bacterial AAA+ proteases.
Item Description:Gesehen am 05.03.2026
Physical Description:Online Resource
ISSN:2399-3642
DOI:10.1038/s42003-025-08908-w

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