PXD015752

PXD015752 is an original dataset announced via ProteomeXchange.

Title	Arg-GlcNAcylation of GshB, An intra-bacterial activity for a T3SS effector
Description	Many Gram-negative bacterial pathogens interact with mammalian cells by using type III secretion systems (T3SS) to inject virulence proteins directly into infected host cells. A subset of these injected protein ‘effectors’ are enzymes that modify the structure and inhibit the function of human proteins by catalyzing the addition of unusual post-translational modifications. T3SS effectors play essential roles in bacterial virulence and their modes of action have provided great insight into the functions and the components of the innate immune system. The E. coli and Citrobacter rodentium NleB effectors, as well as the Salmonella enterica SseK effectors are glycosyltransferases that modify host protein substrates with N-acetyl glucosamine (GlcNAc) on arginine residues. Arginine glycosylation is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles. This post-translational modification disrupts the normal functioning of host immune response proteins. T3SS effectors are chaperoned in the bacterium to keep the effectors partially unfolded and competent for secretion, as well as for targeting the effectors to the T3SS sorting platform. The chaperones are then stripped from their effector substrates at the sorting platform and the effectors are secreted in an unfolded conformation. T3SS effectors are thought to be inactive within the bacterium and fold into their active conformations after they are injected into host cells. While performing mass spectrometry experiments to identify glycosylation substrates of NleB orthologs, we unexpectedly observed that the E. coli glutathione synthetase (GshB) is glycosylated on an arginine residue (R256) by NleB. NleB glycosyltransferase activity is essential to C. rodentium survival in oxidative stress conditions because glycosylation of GshB results in enhanced glutathione production. These data represent, to our knowledge, the first intra-bacterial activity for a T3SS effector and show that effector activities thought to be restricted to host cell compartments additionally play important roles in regulating bacterial physiology.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:05:47.003.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nichollas Scott
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	complex glycosylation
Instrument	Orbitrap Fusion Lumos; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-09 01:23:48	ID requested
1	2020-01-14 00:00:38	announced
⏵ 2	2024-10-22 04:05:47	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Citrobacter rodentium, EHEC, NleB,Glycosylation, EPEC, effectors

Philip R. Hardwidge
contact affiliation	College of Veterinary Medicine, Kansas State University, Manhattan, KS, United States
contact email	hardwidg@vet.k-state.edu
lab head
Nichollas Scott
contact affiliation	University of Melbourne
contact email	nichollas.scott@unimelb.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/01/PXD015752

PRIDE project URI

• PRIDE
  1. PXD015752
     1. Label: PRIDE project
     2. Name: Arg-GlcNAcylation of GshB, An intra-bacterial activity for a T3SS effector