The listeria monocytogenes persistence factor ClpL is a potent stand-alone disaggregase

• Verfasst von: Bohl, Valentin [VerfasserIn]
• Verfasst von: Hollmann, Nele Merret [VerfasserIn]
• Verfasst von: Melzer, Tobias [VerfasserIn]
• Verfasst von: Katikaridis, Panagiotis [VerfasserIn]
• Verfasst von: Meins, Lena [VerfasserIn]
• Verfasst von: Simon, Bernd [VerfasserIn]
• Verfasst von: Flemming, Dirk [VerfasserIn]
• Verfasst von: Sinning, Irmgard [VerfasserIn]
• Verfasst von: Hennig, Janosch [VerfasserIn]
• Verfasst von: Mogk, Axel [VerfasserIn]
• Titel: The listeria monocytogenes persistence factor ClpL is a potent stand-alone disaggregase
• Verf.angabe: Valentin Bohl, Nele Merret Hollmann, Tobias Melzer, Panagiotis Katikaridis, Lena Meins, Bernd Simon, Dirk Flemming, Irmgard Sinning, Janosch Hennig, Axel Mogk
• E-Jahr: 2024
• Jahr: April 23, 2024
• Umfang: 26 S.
• Fussnoten: Gesehen am 16.09.2024
• Titel Quelle: Enthalten in: eLife
• Ort Quelle: Cambridge : eLife Sciences Publications, 2012
• Jahr Quelle: 2024
• Band/Heft Quelle: 12(2024), Artikel-ID RP92746, Seite 1-26
• ISSN Quelle: 2050-084X
• DOI: doi:10.7554/eLife.92746
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: AAA protein
• Sach-SW: chaperone
• Sach-SW: disaggregation
• Sach-SW: heat resistance
• Sach-SW: heat shock protein
• Sach-SW: proteostasis
• K10plus-PPN: 1902564804

Abstract

Heat stress can cause cell death by triggering the aggregation of essential proteins. In bacteria, aggregated proteins are rescued by the canonical Hsp70/AAA+ (ClpB) bi-chaperone disaggregase. Man-made, severe stress conditions applied during, e.g., food processing represent a novel threat for bacteria by exceeding the capacity of the Hsp70/ClpB system. Here, we report on the potent autonomous AAA+ disaggregase ClpL from Listeria monocytogenes that provides enhanced heat resistance to the food-borne pathogen enabling persistence in adverse environments. ClpL shows increased thermal stability and enhanced disaggregation power compared to Hsp70/ClpB, enabling it to withstand severe heat stress and to solubilize tight aggregates. ClpL binds to protein aggregates via aromatic residues present in its N-terminal domain (NTD) that adopts a partially folded and dynamic conformation. Target specificity is achieved by simultaneous interactions of multiple NTDs with the aggregate surface. ClpL shows remarkable structural plasticity by forming diverse higher assembly states through interacting ClpL rings. NTDs become largely sequestered upon ClpL ring interactions. Stabilizing ring assemblies by engineered disulfide bonds strongly reduces disaggregation activity, suggesting that they represent storage states.