PXD041347

PXD041347 is an original dataset announced via ProteomeXchange.

Title	Bacillus subtilis YtpP and thioredoxin A are new players in the CoA-mediated defense mechanism against cellular stress
Description	Coenzyme A is an important cellular metabolite critical for metabolic processes and the regulation of gene expression. The recent discovery of its antioxidant role has highlighted its protective function that leads to the formation of a mixed-disulfide bond with protein cysteines, termed protein CoAlation. To date, more than 2,000 CoAlated bacterial and mammalian proteins have been identified in cellular response to oxidative stress with the majority being involved in metabolic pathways (60%). In vitro and cellular studies have shown that protein CoAlation is a widespread post-translational modification, which modulates the activity and conformation of the modified proteins. The induction of protein CoAlation by oxidative stress was found to be rapidly reversed after the removal of oxidizing agents from the medium of cultured cells. In this study, we developed an ELISA-based deCoAlation assay to detect deCoAlation activity from B. subtilis and B. megaterium lysates. We then used a combination of ELISA-based assay and purification strategies to show that deCoAlation is an enzyme-driven mechanism. Using mass-spectrometry and deCoAlation assays (anti-CoA WB), we identified B. subtilis YtpP (thioredoxin-like protein) and thioredoxin A (TrxA) as enzymes that can remove CoA from different substrates. With mutagenesis studies, we identified YtpP and TrxA catalytic cysteine residues and proposed a possible deCoAlation mechanism for MsrA and PRDX5, which results in the release of both CoA and the reduced form of MsrA or PRDX5. Overall, this paper reveals deCoAlation activity of YtpP and TrxA, and opens doors to future studies on the CoA-mediated redox regulation of CoAlated proteins under various cellular stress conditions.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:47:37.028.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Skehel
SpeciesList	scientific name: Bacillus subtilis subsp. subtilis str. L170; NCBI TaxID: 536088;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-05 04:01:03	ID requested
1	2023-05-10 14:46:55	announced
⏵ 2	2023-11-14 08:47:46	announced	2023-11-14: Updated project metadata.

Tossounian MA, Baczynska M, Dalton W, Peak-Chew SY, Undzenas K, Korza G, Filonenko V, Skehel M, Setlow P, Gout I, YtpP and Thioredoxin A Are New Players in the Coenzyme-A-Mediated Defense Mechanism against Cellular Stress. Antioxidants (Basel), 12(4):(2023) [pubmed]

submitter keyword: Bacillus megaterium,Coenzyme A, Bacillus subtilis, antioxidant, oxidative stress, mixed-disulfide, protein CoAlation, protein deCoAlation

Ivan Gout
contact affiliation	Department of Structural and Molecular Biology, University College London, London, United Kingdom
contact email	i.gout@ucl.ac.uk
lab head
Mark Skehel
contact affiliation	Francis Crick Institute
contact email	skehelm@crick.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041347
     1. Label: PRIDE project
     2. Name: Bacillus subtilis YtpP and thioredoxin A are new players in the CoA-mediated defense mechanism against cellular stress