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Record W4309862298 · doi:10.7554/elife.76387

EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling

2022· article· en· W4309862298 on OpenAlexaff
Lyra O. Randzavola, Paige M Mortimer, Emma Garside, Elizabeth R. Dufficy, Andrea Schejtman, Georgia Roumelioti, Lu Yu, Mercedes Pardo, Kerstin Spirohn, Charlotte Tolley, Cordelia Brandt, Katherine Harcourt, Esme Nichols, Mike Nahorski, Geoff Woods, James C. Williamson, Shreehari Suresh, John M. Sowerby, Misaki Matsumoto, Célio X.C. Santos, Cher Shen Kiar, Subhankar Mukhopadhyay, William Rae, Gordon J. Dougan, John D. Grainger, Paul J. Lehner, Michael A. Calderwood, Jyoti S. Choudhary, Simon Clare, Anneliese O. Speak, Giorgia Santilli, Alex Bateman, Kenneth G. C. Smith, Francesca Magnani, David Thomas

Bibliographic record

VenueeLife · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAdenosine and Purinergic Signaling
Canadian institutionsInstitute of Cancer Research
FundersBiotechnology and Biological Sciences Research CouncilMedical Research CouncilWellcome TrustWellcome
KeywordsNADPH oxidaseBiologyPhagocyteCell biologyInnate immune systemInflammasomeChronic granulomatous diseaseReactive oxygen speciesAcquired immune systemImmune systemGlycosylationCalreticulinImmunityPhagocytosisReceptorImmunologyBiochemistryEndoplasmic reticulum

Abstract

fetched live from OpenAlex

EROS (essential for reactive oxygen species) protein is indispensable for expression of gp91 phox , 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 phox maturation. It binds the immature 58 kDa gp91 phox directly, preventing gp91 phox 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.072
Threshold uncertainty score0.457

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.228
Teacher spread0.219 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations18
Published2022
Admission routes1
Has abstractyes

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