ORP3 Promotes ALPK1-TIFA Dependent NF-κB Activation upon Detection of Bacterial Heptose Phosphate containing Metabolites
Bibliographic record
Abstract
The innate immune system identifies microbe-associated molecular patterns (MAMPs) via pattern recognition receptors (PRRs). Heptose phosphates (HPs) are bacterial-derived metabolic intermediates of lipopolysaccharide biosynthesis (LPS) and a novel class of MAMP. HPs bind the PRR Alpha kinase 1 (ALPK1) in the cytosol of mammalian cells, triggering TIFA dependent activation of NF-κB. Here I show that Oxysterol binding protein-like 3 (ORP3), originally identified in a screen for HP interactors, facilitates TIFA dependent NF-κB activity in response to HPs. I stably integrated a CRISPR construct into HEK293T cells with small guide RNAs (sgRNAs) targeting OSBPL3. I confirmed the knockout in the resulting monoclonal cell lines by sequencing and immunoblot. I found NF-κB luciferase reporter activity to be significantly reduced upon stimulation with ADP-heptose and heptose-1-phosphate (HMP) in ORP3 knockouts which suggests ORP3 contributes to the ALPK1-TIFA PRR response. I further propose three possibilities which may explain the mechanism by which this occurs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".