PXD006810

PXD006810 is an original dataset announced via ProteomeXchange.

Title	NleB host targets - The bacterial arginine glycosyltransferase effector NleB preferentially modifies Fas-associated death domain protein (FADD)
Description	The inhibition of host innate immunity pathways is essential for the survival of attaching and effacing (A/E) pathogens such as enteropathogenic Escherichia coli (EPEC) and Citrobacter rodentium during mammalian infections. To subvert these pathways, A/E pathogens utilize a type III secretion system (T3SS) to introduce effectors that target key signaling pathways thereby suppressing the anti-microbial response. One effector used by A/E pathogens is the arginine glycosyltransferase NleB1 (NleBCR in C. rodentium) that modifies conserved arginine residues with N-acetylglucosamine (GlcNAc) in death-domain containing host proteins thereby blocking extrinsic apoptosis signaling. When expressed ectopically, NleB1 modifies the host proteins, FADD, TRADD and RIPK1. However, the true repertoire of arginine-GlcNAcylation during infection with endogenous levels of NleB delivered by the pathogen is unknown. Here we explored the effects of arginine-GlcNAcylation by NleB on the global host proteome. Utilizing an affinity proteomic approach for Arginine-GlcNAcylated glycopeptide, we compared the global repertoire of arginine-GlcNAcylation during ectopic expression of NleB, EPEC infection in vitro or C. rodentium infection in vivo. When NleB was overexpressed, multiple host proteins were arginine-GlcNAcylated. However, when endogenous levels of NleB were delivered during EPEC and C. rodentium infection, R117of FADD was rapidly and preferentially modified. The arginine-GlcNAcylation modification of FADD was extremely stable and insensitive to environmental or host cell degradation. Despite its stability and effect on the inhibition of apoptosis, arginine-GlcNAcylation did not illicit any proteomic changes, even in response to prolonged expression of NleB. Thus, under wild type levels of expression, NleB1/NleBCR antagonizes death-receptor-induced apoptosis of infected cells by modifying FADD in an irreversible and silent manner.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:38:23.193.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nichollas Scott
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	complex glycosylation
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-06-27 06:17:36	ID requested
1	2017-09-11 01:51:34	announced
⏵ 2	2024-10-22 04:38:25	announced	2024-10-22: Updated project metadata.

10.1074/jbc.m117.805036;

Scott NE, Giogha C, Pollock GL, Kennedy CL, Webb AI, Williamson NA, Pearson JS, Hartland EL, The bacterial arginine glycosyltransferase effector NleB preferentially modifies Fas-associated death domain protein (FADD). J Biol Chem, 292(42):17337-17350(2017) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: EPEC,NleB

Elizabeth Hartland
contact affiliation	Department of Microbiology and Immunology, University of Melbourne Peter Doherty Institute for Infection and Immunity 792 Elizabeth St, Melbourne 3000, Australia
contact email	Hartland@unimelb.edu.au
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/2017/09/PXD006810

PRIDE project URI

• PRIDE
  1. PXD006810
     1. Label: PRIDE project
     2. Name: NleB host targets - The bacterial arginine glycosyltransferase effector NleB preferentially modifies Fas-associated death domain protein (FADD)