PXD053520

PXD053520 is an original dataset announced via ProteomeXchange.

Title	A Leishmania virulence factor harnesses an allosteric kinase switch to regulate its ubiquitin ligase activity
Description	Stringent control of ubiquitylation is a central requirement of signaling specificity in eukaryotes. Here, we discover a domain module integrating protein kinase and ubiquitin ligase domains within a single protein. This module is widespread across unicellular eukaryotic lineages and particularly conserved in Leishmania, the causative agents of major neglected tropical diseases with a strong therapeutic need. We reveal that a gene encoding the module, TKUL, is essential for L. mexicana to sustain macrophage infections and that TKUL can cooperate with HSP70 to modify unfolded proteins with degradative ubiquitin chains. Intriguingly, the HECT-type ubiquitin ligase activity of TKUL requires its atypical kinase domain, with kinase autophosphorylation triggering activating conformational changes across the catalytic module. Consistent with the ligase domain harnessing the kinase domain for regulation, TKUL-driven ubiquitylation can allosterically be suppressed by small-molecule kinase inhibitors. Together, this work establishes an unprecedented allosteric coupling mechanism in the realms of phosphorylation and ubiquitylation.
HostingRepository	PRIDE
AnnounceDate	2025-09-22
AnnouncementXML	Submission_2025-09-22_06:47:44.444.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	F Butter
SpeciesList	scientific name: Trypanosoma brucei; NCBI TaxID: 5691;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-30 06:30:40	ID requested
⏵ 1	2025-09-22 06:47:44	announced

Dataset with its publication pending

submitter keyword: LC-MS/MS

Falk Butter
contact affiliation	Institute of Molecular Biology (IMB)
contact email	f.butter@imb.de
lab head
F Butter
contact affiliation	Quantitative Proteomics Institute of Molecular Biology (IMB)
contact email	f.butter@imb-mainz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053520
     1. Label: PRIDE project
     2. Name: A Leishmania virulence factor harnesses an allosteric kinase switch to regulate its ubiquitin ligase activity