Enzymes | Clp Proteases

Beardslee, Patrick C.; Dhamdhere, Gaury; Jiang, Jialiu; Ogbonna, Emmanuel C.; Presloid, Christopher J.; Prorok, Monika; Bheemreddy, Priyanka; Sullivan, Christian D.; Vorn, Jennifer; Schmitz, Karl R.

doi:10.1016/b978-0-12-819460-7.00156-0

Cited by 2 publications

(4 citation statements)

References 161 publications

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“…ClpC1 is composed of a globular N-terminal domain that binds to substrates and adaptors and an ATPase core consisting of two AAA+ modules that carry out chemomechanical substrate unfolding and translocation ( 8 , 10 , 80 – 82 ). Surprisingly, our studies identified few interaction partners that bind exclusively to either the NTD or the ATPase core.…”

Section: Discussionmentioning

confidence: 99%

“…Clp proteases are well-studied proteolytic machines that unravel and hydrolyze native protein substrates ( 8 , 9 ). These large oligomeric complexes consist of a hexameric Clp unfoldase that recognizes substrates, unfolds them using energy from ATP hydrolysis, and spools them into an associated peptidase barrel for degradation ( 10 ). The mycobacterial Clp peptidase is composed of two paralogous heptamers, ClpP1 and ClpP2, that assemble into a catalytically active hetero-oligomeric ClpP1P2 tetradecamer ( 11 – 16 ).…”

Section: Introductionmentioning

confidence: 99%

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Interactome Analysis Identifies MSMEI_3879 as a Substrate of Mycolicibacterium smegmatis ClpC1

et al. 2023

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interactome Analysis Identifies MSMEI_3879 as a Substrate of Mycolicibacterium smegmatis ClpC1

et al. 2023

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“…ClpC1 is composed of a globular N-terminal domain that binds to substrates and adaptors, and an ATPase core consisting of two AAA+ modules that carry out chemomechanical substrate unfolding and translocation (8, 10, 85–87). Surprisingly, our studies identified few interaction partners that bind exclusively to either the NTD or the ATPase core.…”

Section: Discussionmentioning

confidence: 99%

“…Clp proteases are well studied proteolytic machines that unravel and hydrolyze native protein substrates(8, 9). These large oligomeric complexes consist of a hexameric Clp unfoldase that recognizes substrates, unfolds them using energy from ATP hydrolysis, and spools them into an associated peptidase barrel for degradation (10). The mycobacterial Clp peptidase is composed of two paralogous heptamers, ClpP1 and ClpP2, that assemble into a catalytically active hetero-oligomeric ClpP1P2 tetradecamer (11–16).…”

Section: Introductionmentioning

confidence: 99%

Interactome analysis identifies MSMEI_3879 as a substrate ofMycolicibacterium smegmatisClpC1

Ogbonna

Bheemreddy

Schmitz

2022

Preprint

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The prevalence of drug resistant Mycobacterium tuberculosis infections has prompted extensive efforts to exploit new mycobacterial drug targets. ClpC1, the unfoldase component of the essential ClpC1P1P2 protease, has emerged as one particularly promising antibacterial target. However, efforts to identify and characterize ClpC1-targeting compounds are constrained by our limited knowledge of Clp protease function and regulation. To expand our understanding of ClpC1 physiology, we employed a co-immunoprecipitation and mass spectrometry workflow to identify proteins that interact with ClpC1 in Mycolicibacterium smegmatis, a relative of M. tuberculosis. We identify a diverse panel of interaction partners, many of which make co-immunoprecipitate with both the regulatory N-terminal domain and the ATPase core of ClpC1. Notably, our interactome analysis identifies MSMEI_3879, a truncated gene product unique to M. smegmatis, as a novel proteolytic substrate. Degradation of MSMEI_3879 by ClpC1P1P2 in vitro requires an exposed N-terminal sequence, reinforcing the idea that ClpC1 selectively recognizes disordered motifs. Fluorescent substrates incorporating MSMEI_3879 may be useful in screening for novel ClpC1-targeting antibiotics, to help address the challenge of M. tuberculosis drug resistance.

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Enzymes | Clp Proteases

Cited by 2 publications

References 161 publications

Interactome Analysis Identifies MSMEI_3879 as a Substrate of Mycolicibacterium smegmatis ClpC1

Interactome Analysis Identifies MSMEI_3879 as a Substrate of Mycolicibacterium smegmatis ClpC1

Interactome analysis identifies MSMEI_3879 as a substrate ofMycolicibacterium smegmatisClpC1

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