Identification of a novel motif in MARCH1 that affects the conformation and the E3 ubiquitin ligase activity (65.10)
Bibliographic record
Abstract
Abstract Some members of the MARCH family of RING-type E3 ubiquitin ligases target important players of immune responses. Of these, MARCH1 prevents the cell surface accumulation of MHC class II molecules and regulates antigen presentation in response to IL-10 in human primary monocytes (Thibodeau et. al., Eur JI 2008). Structure-function analysis of mouse MARCH1 showed the presence of two functional tyrosine-based endosomal sorting motifs in the C-terminal cytoplasmic part of the protein. We investigated the importance of the corresponding motifs in human MARCH1. Site-directed mutagenesis of these tyrosines did not reduce the activity of MARCH1 in transfected cells. However, a reporter molecule fused to the C-terminal cytoplasmic domain of MARCH1 was expressed less efficiently at the plasma membrane. A series of deletions were made in the C-terminal part of MARCH1 and a new functional motif was discovered. BRET experiments revealed that this motif is important for the spatial organisation of the two cytoplasmic domains of MARCH1. Interestingly, this motif is also present in others RING-type E3 ubiquitin ligases such as Parkin and its alteration is linked to the development of the disease in certain patients.
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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 | 0.001 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".