PXD070650

PXD070650 is an original dataset announced via ProteomeXchange.

Title	Membrane-associated effluxosomes coordinate multi-metal resistance in Mycobacterium tuberculosis
Description	Bacterial pathogens must withstand metal-induced stress during infection, yet the mechanisms by which they sense and respond to toxic metal ions remain incompletely understood. Here, we uncover a previously unrecognized mechanism in Mycobacterium tuberculosis, the causative agent of tuberculosis, which assembles dynamic, membrane-associated platforms organized by PacL proteins to mediate resistance to multiple metals. The small membrane-associated proteins PacL1, PacL2, and PacL3 coordinate the clustering of P-type ATPase pumps, namely CtpC, CtpG, and CtpV, into functional complexes that we term effluxosomes. Using single-particle tracking, we reveal distinct dynamic populations, with highly mobile PacL proteins integrating into more slowly mobile effluxosomes. PacL proteins stabilize CtpC and CtpG within these assemblies, promoting cross-resistance to zinc and cadmium, with PacL1 acting as a multi-substrate metallochaperone that binds zinc, cadmium, and copper via a conserved C-terminal motif. Single molecule-based super-resolution microscopy shows that conserved residues within the PacL transmembrane domain are essential for effluxosome assembly. Strikingly, proximity labeling reveals a broad PacL1 interaction network, suggesting that effluxosomes contribute to a wider stress adaptation program. These findings establish effluxosomes as dynamic membrane machineries that orchestrate coordinated multi-metal resistance in M. tuberculosis, opening new avenues for antimicrobial targeting. This native MS dataset assesses the metal binding properties of different PacL constructs.
HostingRepository	PRIDE
AnnounceDate	2025-12-15
AnnouncementXML	Submission_2025-12-15_06:34:26.018.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Julien Marcoux
SpeciesList	scientific name: Mycobacterium tuberculosis H37Rv; NCBI TaxID: NEWT:83332;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-12 14:29:26	ID requested
⏵ 1	2025-12-15 06:34:26	announced

Dataset with its publication pending

submitter keyword: metal binding, tuberculosis,native MS

Julien Marcoux
contact affiliation	ProteoToul, Institute of Pharmacology and Structural Biology (IPBS), CNRS, Toulouse
contact email	julien.marcoux@ipbs.fr
lab head
Julien Marcoux
contact affiliation	IPBS
contact email	julien.marcoux@ipbs.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD070650
     1. Label: PRIDE project
     2. Name: Membrane-associated effluxosomes coordinate multi-metal resistance in Mycobacterium tuberculosis