PXD030385

PXD030385 is an original dataset announced via ProteomeXchange.

Title	Interactome analysis by shotgun proteomics identifies a novel substrate for Mycolicibacterium smegmatis unfoldase ClpC1
Description	Tuberculosis remains a leading cause of worldwide infectious mortality and one of the top ten leading causes of death overall. While advances in public health have contributed to a reduction in tuberculosis cases, the prevalence of multidrug-resistant Mycobacterium tuberculosis (Mtb) (MDR-TB) infections has created an urgent need to exploit novel drug targets. One such target is the ClpC1P1P2 protease, which degrades folded cytosolic proteins through the cooperation of the ATP-dependent unfoldase ClpC1 and the ClpP1P2 peptidase. Both protease components are strictly essential for Mtb viability and are validated therapeutic targets. However, efforts to develop anti-Mtb compounds are constrained by a limited understanding of Clp protease function and essentiality. Thus, it is crucial to identify physiological substrates and pathways regulated by this protease. In this study, we identify cellular proteins that interact with the ClpC1 unfoldase in Mycolicibacterium smegmatis (Msm), a nonpathogenic surrogate for Mtb. Using a FLAG-tagged ClpC1 variant with mutations within the Walker B motifs, candidate ClpC1 interaction partners were captured by co-immunoprecipitation and identified by mass spectrometry-based proteomics (LC-MS/MS). Notably, our work reveals a novel proteolytic substrate, 5-oxoprolinase, which is recognized by ClpC1P1P2 via an N-terminal degradation sequence.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:01:45.055.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD030385
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Emmanuel Ogbonna
SpeciesList	scientific name: Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155); NCBI TaxID: 246196;
ModificationList	iodoacetic acid derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-14 01:40:26	ID requested
1	2022-12-12 14:24:18	announced
2	2023-06-23 08:14:27	announced	2023-06-23: Updated project metadata.
⏵ 3	2023-11-14 09:01:50	announced	2023-11-14: Updated project metadata.

10.6019/PXD030385;

Ogbonna EC, Anderson HR, Beardslee PC, Bheemreddy P, Schmitz KR, Interactome Analysis Identifies MSMEI_3879 as a Substrate of Mycolicibacterium smegmatis ClpC1. Microbiol Spectr, 11(4):e0454822(2023) [pubmed]

submitter keyword: Clp protease, unfoldase ClpC1, shotgun proteomics, tuberculosis,Mycolicibacterium smegmatis

Karl Robert Schmitz
contact affiliation	Department of Biological Sciences, Department of Chemistry & Biochemistry University of Delaware Newark DE, 19716
contact email	schmitzk@udel.edu
lab head
Emmanuel Ogbonna
contact affiliation	University of Delaware
contact email	eogbonna@udel.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030385
     1. Label: PRIDE project
     2. Name: Interactome analysis by shotgun proteomics identifies a novel substrate for Mycolicibacterium smegmatis unfoldase ClpC1