PXD022384

PXD022384 is an original dataset announced via ProteomeXchange.

Title	MDP phosphorylation by NAGK is essential for NOD2 activation
Description	Bacterial cell wall components provide various unique molecular structures that are detected by pattern recognition receptors (PRRs) of the innate immune system as non-self. Most bacterial species form a cell wall that consists of peptidoglycan, a polymeric structure comprising of alternating amino sugars. Muramyl dipeptide (MDP) is the minimal, biologically active molecular structure derived from peptidoglycan, and its immunogenicity is well documented in numerous studies. MDP is sensed by the cytosolic nucleotide-binding and nucleotide oligomerization domain-like receptor 2 (NOD2), which triggers a pro-inflammatory response upon engagement 1,2. Conducting a forward genetic screen to identify factors required for MDP detection, we discovered that N-acetylglucosamine kinase (NAGK) is essential for the immunostimulatory activity of MDP. NAGK, which has previously been identified to contribute to the hexosamine salvage pathway in humans, is broadly expressed and inducible in innate immune cells. Mechanistically, NAGK functions upstream of NOD2 in that it directly phosphorylates the N-acetylmuramic moiety of MDP at the hydroxyl group of its C6 position, yielding 6-O-phospho-MDP. NAGK-phosphorylated MDP constitutes an essential component of NOD2 dependent signal transduction. Altogether, these results unveil a previously unknown interconnection of amino sugar metabolism and innate immunity to bacterial cell walls.
HostingRepository	PRIDE
AnnounceDate	2022-06-21
AnnouncementXML	Submission_2022-06-21_06:25:21.004.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-05 06:10:07	ID requested
⏵ 1	2022-06-21 06:25:21	announced

Boyle JP, Parkhouse R, Monie TP, Insights into the molecular basis of the NOD2 signalling pathway. Open Biol, 4(12):(2014) [pubmed]

submitter keyword: NOD2, Muramyl dipeptide, inflammation, bacterial sensing, NAGK, sugar kinase

Matthias Mann
contact affiliation	Department of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Germany
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022384
     1. Label: PRIDE project
     2. Name: MDP phosphorylation by NAGK is essential for NOD2 activation