PXD067990-1

PXD067990 is an original dataset announced via ProteomeXchange.

Title	Multiple aspartic proteases process PE and PPE proteins on the mycobacterial surface of pathogenic mycobacteria
Description	Mycobacterium tuberculosis is the world’s leading bacterial infectious agent. The absence of an effective vaccine and the rise of multi-drug resistant M. tuberculosis strains emphasize the need to identify novel targets for prevention and intervention strategies. Previously, the M. marinum orthologue of the aspartic protease PecA (PE_PGRS35) was found on the bacterial cell surface of the pathogenic strain M. marinum, after secretion by the specialized type VII secretion system. PecA was shown to be responsible for the processing of secreted PE_PGRS proteins, including itself. Both M. marinum and M. tuberculosis encode two additional predicted aspartic proteases with similar secretion domains (PE_PGRS16 and PE26). In this study, the roles of the M. marinum PecA, PecB and PecC were studied using frameshift mutants generated by CRISPR-Cas9 technology. Numerous PecA substrates were identified using analysis of semi-tryptic peptides detected by proteomics of secreted, surface-associated protein fractions. The most abundant substrates are members of the PE and PPE protein families. In addition, analysis of semi-tryptic peptides revealed consensus cleavage sites. Interestingly, these cleavage sites were often located within the Type VII secretion motif (YxxxD/E) and thereby effectively removing the entire PE domain. PecB and PecC were also predicted to process PE and PPE proteins, although to a lesser extent than PecA. Follow-up experiments revealed that also PecC is involved in processing of a small subset of the PPE protein family. Finally, our evidence indicates that PecA plays a similar role in M. tuberculosis, as PecA is also responsible for cleavage of PE_PGRS proteins in this species.
HostingRepository	PRIDE
AnnounceDate	2026-08-19
AnnouncementXML	Submission_2026-08-19_02:30:15.269.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thang Pham
SpeciesList	scientific name: Mycobacterium marinum ATCC BAA-535; NCBI TaxID: NEWT:1348799;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-02 05:58:23	ID requested
⏵ 1	2026-08-19 02:30:16	announced

Meijers AS, Gallant JL, Speer A, Maaskant J, Hietam, ä, ki S, Ummels R, Paulu, ß, en FM, Grossmann TN, Pham TV, Piersma SR, Jim, é, nez CR, Nejentsev S, Bitter W, Kuijl CP, Multiple aspartic proteases process PE and PPE proteins on the mycobacterial surface of pathogenic mycobacteria. J Biol Chem, 302(10):113450(2026) [pubmed]

10.1016/j.jbc.2026.113450;

submitter keyword: mycobacterium marinum, Aspartic acid protease, substrate specificity

Connie Jimenez
contact affiliation	Connie Jimenez, OncoProteomics Laboratory, Dept of Medical Oncology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
contact email	c.jimenez@amsterdamumc.nl
lab head
Thang Pham
contact affiliation	Amsterdam UMC
contact email	t.pham@amsterdamumc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD067990
     1. Label: PRIDE project
     2. Name: Multiple aspartic proteases process PE and PPE proteins on the mycobacterial surface of pathogenic mycobacteria