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dc.contributor.authorRandzavola, LO
dc.contributor.authorMortimer, PM
dc.contributor.authorGarside, E
dc.contributor.authorDufficy, ER
dc.contributor.authorSchejtman, A
dc.contributor.authorRoumelioti, G
dc.contributor.authorYu, L
dc.contributor.authorPardo, M
dc.contributor.authorSpirohn, K
dc.contributor.authorTolley, C
dc.contributor.authorBrandt, C
dc.contributor.authorHarcourt, K
dc.contributor.authorNichols, E
dc.contributor.authorNahorski, M
dc.contributor.authorWoods, G
dc.contributor.authorWilliamson, JC
dc.contributor.authorSuresh, S
dc.contributor.authorSowerby, JM
dc.contributor.authorMatsumoto, M
dc.contributor.authorSantos, CXC
dc.contributor.authorKiar, CS
dc.contributor.authorMukhopadhyay, S
dc.contributor.authorRae, WM
dc.contributor.authorDougan, GJ
dc.contributor.authorGrainger, J
dc.contributor.authorLehner, PJ
dc.contributor.authorCalderwood, MA
dc.contributor.authorChoudhary, J
dc.contributor.authorClare, S
dc.contributor.authorSpeak, A
dc.contributor.authorSantilli, G
dc.contributor.authorBateman, A
dc.contributor.authorSmith, KGC
dc.contributor.authorMagnani, F
dc.contributor.authorThomas, DC
dc.date.accessioned2023-01-24T13:41:12Z
dc.date.available2023-01-24T13:41:12Z
dc.date.issued2022-11-24
dc.identifierARTN e76387
dc.identifier.citationeLife, 2022, 11en_US
dc.identifier.issn2050-084X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5664
dc.identifier.eissn2050-084X
dc.identifier.eissn2050-084X
dc.identifier.doi10.7554/eLife.76387
dc.identifier.doi10.7554/eLife.76387
dc.description.abstract<jats:p>EROS (essential for reactive oxygen species) protein is indispensable for expression of gp91<jats:italic>phox</jats:italic>, the catalytic core of the phagocyte NADPH oxidase. EROS deficiency in humans is a novel cause of the severe immunodeficiency, chronic granulomatous disease, but its mechanism of action was unknown until now. We elucidate the role of EROS, showing it acts at the earliest stages of gp91<jats:italic>phox</jats:italic> maturation. It binds the immature 58 kDa gp91<jats:italic>phox</jats:italic> directly, preventing gp91<jats:italic>phox</jats:italic> degradation and allowing glycosylation via the oligosaccharyltransferase machinery and the incorporation of the heme prosthetic groups essential for catalysis. EROS also regulates the purine receptors P2X7 and P2X1 through direct interactions, and P2X7 is almost absent in EROS-deficient mouse and human primary cells. Accordingly, lack of murine EROS results in markedly abnormal P2X7 signalling, inflammasome activation, and T cell responses. The loss of both ROS and P2X7 signalling leads to resistance to influenza infection in mice. Our work identifies EROS as a highly selective chaperone for key proteins in innate and adaptive immunity and a rheostat for immunity to infection. It has profound implications for our understanding of immune physiology, ROS dysregulation, and possibly gene therapy.</jats:p>
dc.languageEnglish
dc.language.isoengen_US
dc.publishereLIFE SCIENCES PUBL LTDen_US
dc.relation.ispartofeLife
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectBiology
dc.subjectLife Sciences & Biomedicine - Other Topics
dc.subjectNADPH oxidase
dc.subjectchaperone
dc.subjectinflammasome
dc.subjectP2X receptor
dc.subjectOST complex
dc.subjectT cells
dc.subjectMouse
dc.subjectCHRONIC GRANULOMATOUS-DISEASE
dc.subjectCYTOCHROME B(558)
dc.subjectFLAVOCYTOCHROME B(558)
dc.subjectRESPIRATORY BURST
dc.subjectRECEPTOR
dc.subjectPROTEIN
dc.subjectNEUTROPHILS
dc.subjectACTIVATION
dc.subjectBIOSYNTHESIS
dc.subjectEXPRESSION
dc.titleEROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signallingen_US
dc.typeJournal Article
dcterms.dateAccepted2022-10-31
dc.date.updated2023-01-24T13:22:39Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.7554/eLife.76387en_US
rioxxterms.licenseref.startdate2022-11-24
rioxxterms.typeJournal Article/Reviewen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Functional Proteomics Group
pubs.publication-statusPublished
pubs.publisher-urlhttp://dx.doi.org/10.7554/elife.76387
pubs.volume11
icr.researchteamFunctional Proteomicsen_US
dc.contributor.icrauthorPardo Calvo, Maria Mercedes
icr.provenanceDeposited by Dr Mercedes Pardo Calvo on 2023-01-24. Deposit type is initial. No. of files: 1. Files: elife-Eros.pdf


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