PXD065654

PXD065654 is an original dataset announced via ProteomeXchange.

Title	Structural Insights into Mycobacterial Protein-Mannosyltransferase: Evidence of a WW-Domain-Like Substrate Recognition Mechanism.
Description	We have previously demonstrated that protein-O-mannosylation (POM), a widespread post-translational glycosyl modification of proteins, is a key virulence factor of Mycobacterium tuberculosis (Mt), the world’s deadliest infectious agent. Here, we report a detailed analysis of the structure-function relationship of MtPMT, the enzyme that catalyzes POM in Mtb. Using mutagenesis and in cellulo monitoring of POM activity, we demonstrate that, despite notable structural differences, MtPMT shares functional homologies with yeasts’ PMTs in the mechanism of the sugar transfer from lipidic donors. Furthermore, we provide evidence that the selectivity for proline-rich target glycosylation sites that differentiates MtPMT from its eukaryotic homologues, relies on a WW-like domain, which preferentially interacts with proline-rich acceptor substrate analogues. This first identification of a functional WW-like domain in a prokaryotic protein raises questions about its potential evolutionary linkage with eukaryotic WW modules and provides new insights into PMT’s acceptor-substrate recognition mechanism paving the way for the development selective inhibitors of MtPMT with potential therapeutic application against tuberculosis. This dataset consists in the entire protein analysis of the Fasciclin reporter protein produced in a strain of Mycobacterium smegmatis (Ms) devoid of MsPMT (ΔMsPMT) and expressing either WT-MtPMT, mCherry-Nter-MtPMT or MtPMT-Cter-PhoA.
HostingRepository	PRIDE
AnnounceDate	2025-07-22
AnnouncementXML	Submission_2025-07-22_00:45:48.064.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Julien Marcoux
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	mannosylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-01 04:44:45	ID requested
⏵ 1	2025-07-22 00:45:48	announced

Dataset with its publication pending

submitter keyword: glycosylation,Entire Protein Analysis, protein-O-mannosylation, glycoprotein

Julien Marcoux
contact affiliation	ProteoToul, Institute of Pharmacology and Structural Biology (IPBS), CNRS, Infrastructure Nationale de Protéomique, ProFI, FR 2048, 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. PXD065654
     1. Label: PRIDE project
     2. Name: Structural Insights into Mycobacterial Protein-Mannosyltransferase: Evidence of a WW-Domain-Like Substrate Recognition Mechanism.