PXD025149-2

PXD025149 is an original dataset announced via ProteomeXchange.

Title	EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling.
Description	The phagocyte NADPH oxidase is critical for host defence, and EROS (Essential for Reactive Oxygen Species) protein is indispensable for expression of its gp91phox-p22phox heterodimer. EROS deficiency in humans is a recently described cause of chronic granulomatous disease (CGD), but its mechanism of action remains unknown. We show EROS binds the immature 58kDa gp91phox directly prior to glycosylation and heme incorporation, thus preventing its degradation. EROS interacts with the oligosaccharyl transferase complex (OST) present at the endoplasmic reticulum. Inhibition of the OST complex suppresses EROS-mediated stabilisation of the 58kDa, providing insight into the early steps of gp91phox biosynthesis. EROS also regulates the purine receptors P2X7 and P2X1 through direct interactions. Accordingly, lack of EROS results in markedly abnormal P2X7 signalling, inflammasome activation and T cell responses. The loss of both the phagocyte respiratory burst and P2X7 signalling lead to resistance to influenza infection. Our work identifies EROS as the first described highly selective chaperone controlling key proteins in innate and adaptive immunity. It has profound implications for immune physiology, immunodeficiency and gene therapy.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:52:50.966.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	James Williamson
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-01 06:45:56	ID requested
1	2022-11-30 03:18:24	announced
⏵ 2	2023-11-14 08:52:51	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: NOX family, inflammasome,NADPH oxidase, OST complex, chaperone, T cells, P2X receptor, ER

Paul Lehner
contact affiliation	Cambridge Institute of Therapeutic Immunology and Infectious Disease, Univeristy of Cambridge, UK
contact email	pjl30@cam.ac.uk
lab head
James Williamson
contact affiliation	University of Cambridge
contact email	jcw76@cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025149
     1. Label: PRIDE project
     2. Name: EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling.