Molecular characterization of the interaction between the rheumatoid arthritis shared epitope and calreticulin (144.7)
Bibliographic record
Abstract
Abstract Calreticulin (CRT) is a versatile endoplasmic reticulum protein also known as a cell surface receptor for several innate immune system ligands. We have recently reported that the rheumatoid arthritis (RA) shared epitope (SE), a major risk factor for severe RA, acts as a ligand that specifically binds to CRT and activates innate signaling in other cells. To gain better insights into the molecular characteristics of SE-CRT interaction, here, we have mapped the binding site of the SE ligand on CRT. Experiments with CRT domain-deleted mutants and a sulfo-SBED (sulfosuccinimidyl-2-[6-(biotinamido)-2-(p-azido-benzamido) hexanoamido] ethyl-1,3-dithiopropionate) chemical labeling method localized the SE binding site at the CRT P-domain. Computer-assisted 3D docking predicted the region 217-224 in the CRT P-domain as a potential SE binding site. Finally, site-directed mutagenesis demonstrated involvement of residues Glu217 and Glu223 in both cell-free binding and signal transduction assays. We conclude that the region encompassing amino acid residues 217-223 in the CRT P-domain is a binding site of the RA SE, with critical roles played by residues Glu217 and Glu223, which interact with SE residues Gln70 and Arg72, respectively. The SE binding site is distinct from those previously reported for other CRT ligands. The pathogenic implications of the findings will be discussed.
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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".