Structure-Function Study of the Extracellular Domain of the Human Type I Interferon Receptor (IFNAR)-1 Subunit
Bibliographic record
Abstract
Despite accumulating information about the different effector molecules and signaling cascades that are invoked on interferon-alpha (IFN-alpha) binding to the type 1 IFN receptor, little is known about the specifics of the binding interactions between the ligand and the receptor complex. The IFN-alpha/beta receptor (IFNAR)-2 subunit of the IFN receptor is considered the primary binding chain of the receptor, yet it is clear that both receptor subunits, IFNAR-1 and IFNAR-2, cooperate in the high-affinity binding of IFN to the receptor complex. Earlier results from our laboratory suggested that an association of IFNAR-1 with membrane Galalpha1-4Gal-containing glycolipids facilitates receptor-mediated signaling. The data implicated amino acid residues in the SD100 domain of IFNAR-1 in the glycosphingolipid (GSL) modification of the type 1 IFN receptor. Interestingly, the human and murine counterparts of IFNAR-1 exhibit remarkable species specificity despite their considerable amino acid sequence identity. Certainly, those amino acid residues that effect GSL modification of IFNAR-1 are conserved between species, yet specific regions of IFNAR-1 that confer species specificity have not been defined. To delineate further the role of the IFNAR-1 SD100A domain in receptor function, a chimeric cDNA was assembled, in which the SD100A domain of the murine IFNAR-1 chain was replaced with the human sequence. This construct was expressed in IFNAR-1-/- mouse embryonic fibroblasts, and stable transfectants were established. Transfectants are fully sensitive to murine IFN-alpha4 treatment with respect to the induction of IFN-stimulated gene factor 3 (ISGF3) and sis-inducing factor (SIF) signal transducer and activator of transcription factor (Stat) complexes, exhibiting comparable levels of Stat activation to those observed in IFNAR-1-/- cells reconstituted with intact MuIFNAR-1. Similar results were obtained with IFN-induced antiviral and growth inhibitory responses. Viewed together, these data suggest that the SD100A domain of IFNAR-1 does not contribute to species-specific IFN binding.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
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".