Structural Studies of Histone H3K36 Methyltransferase NSD1 and CRL2 Substrate Receptors FEM1B/C
Bibliographic record
Abstract
NSD1 is a histone methyltransferase that adds one or two methyl groups to H3K36. Mutations of NSD1 result in Soto’s Syndrome, a neurological disease. FEM1B and FEM1C, substrate receptors of ubiquitin ligase CRL2, specifically recognize proteins with an arginine residue at their C-termini. Dysfunction leads to diseases like Alzheimer’s or ALS. To better understand the disease implications of these proteins, this thesis aims to determine the protein structures of the NSD1 variants (Y1869C/T1927A) and FEM1B/FEM1C in complex with their inhibitors, H3K36M or EN106, respectively. Two crystal structures, NSD1(Y1869C) (PDB 8FBG) and NSD1(T1927A) (PDB 8FBH), have been obtained, which contain the cofactor SAM but not H3K36M. The FEM1B(aa 1-356) and FEM1C(aa 1-244) structures have also been reproduced, but lack the presence of EN106. In the future, the wild-type or mutated nucleosome will be used as substrates in the NSD1 co-crystallization, and more potent FEM1B/C inhibitors would be identified to facilitate co-crystallization.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 | 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".