PXD058408

PXD058408 is an original dataset announced via ProteomeXchange.

Title	A Phage Protein Kinase Subverts Bacterial Defense Systems through Hyperpromiscuous Phosphorylation
Description	Bacteria and bacteriophages are in a constant arms race to develop bacterial defense and phage counter-defense systems. The prevailing view so far has been that phage counter-defense systems target specific bacterial defense systems. Here, we uncover a mechanism by which the T7 bacteriophage broadly manipulates host anti-phage defenses using protein phosphorylation. We show that the T7 protein kinase (gene 0.7, or T7K), which was believed to be specific to a defined set host factors, is in fact a hyperpromiscuous dual-specifity kinase enacting a massive wave of phosphorylation on virtually all host and phage proteins during infection. The scale of phosphorylation vastly exceeds the number of previously known phosphorylation events in E. coli, has no sequence motif specificity, and results in a higher proteome-wide phosphorylation density than even in mammalian cells that have ~500 kinases. Stoichiometry analysis of phosphorylation sites revealed a striking bias of T7K activity towards nucleic acid-binding substrates, which we show is mediated by a DNA-binding domain within T7K. This specificity for high stoichiometry phosphorylation of DNA binding proteins enables deactivation of diverse DNA targeting anti-defense systems. We provide mechanistic insight into how T7K weakens the Eco9 bacterial defense system through specific phosphorylation events, with phosphomimetic mutations in key sites of the toxin protein RcaT deactivating its defense. Finally, screening a genetically diverse collection of E. coli strains showed that half of strains with evidence of defense against T7 are also sensitive to T7K demonstrating a high prevalence and significance of T7K-mediated host interactions in nature.
HostingRepository	PRIDE
AnnounceDate	2026-06-17
AnnouncementXML	Submission_2026-06-17_10:57:39.465.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tara Bartolec
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: NEWT:562;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Exploris 480; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-29 04:45:27	ID requested
⏵ 1	2026-06-17 10:57:39	announced

Dataset with its publication pending

submitter keyword: Phosphoproteomics, Phage, Defense systems

Mikhail Savistki
contact affiliation	European Molecular Biology Laboratory Heidelberg
contact email	mikhail.savitski@embl.de
lab head
Tara Bartolec
contact affiliation	EMBL Heidelberg
contact email	tarabartolec@live.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058408
     1. Label: PRIDE project
     2. Name: A Phage Protein Kinase Subverts Bacterial Defense Systems through Hyperpromiscuous Phosphorylation