Identification of N- and C-Terminal Residues Involved in MAP Kinase Phosphatase 3 (MKP3) Interdomain Binding and Auto-Inhibition
Bibliographic record
Abstract
Interdomain binding has been shown to play an important role in the regulation of MAP kinase phosphatase 3 (MKP3), a phosphatase involved in control of ERK signalling pathways. In this study the residues in N- and C-terminal domains responsible for MKP3 interdomain binding are identified. Peptides from the N-terminal substrate-binding domain of MKP3 were assessed for their ability to bind the C-terminal catalytic domain using surface plasmon resonance. The data indicate that the residues 77-97 (the Post-KIM peptide) in the MKP3 N-terminal domain are responsible for its binding to the C-terminal catalytic domain. Residues in the C-terminal domain that might be important to interdomain binding were identified using data in the existing literature. Variants in which these residues had been altered were examined by circular dichroism and enzymatic assays to ensure retention of their structure and catalytic properties before being assessed for their ability to bind the Post-KIM peptide. The data show that glutamic acid 248, asparagine 267 and, to a lesser extent, arginine 299 are important for the interaction between the MKP3 C-terminal and the N-terminal domains. The identified residues map to a region on the surface of the C-terminal domain that appears complementary to the N-terminal domain surface defined by the Post-KIM peptide. This interdomain binding site is distinct from the substrate interaction sites.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".