Solution Structure of the Carboxyl-Terminal Domain of RAP74 and NMR Characterization of the FCP1-Binding Sites of RAP74 and Human TFIIB<sup>,</sup>
Bibliographic record
Abstract
FCP1 (TFIIF-associated CTD phosphatase) is the only known phosphatase specific for the phosphorylated CTD of RNAP II. The phosphatase activity of FCP1 is strongly enhanced by the carboxyl-terminal domain of RAP74 (cterRAP74, residues 436-517), and this stimulatory effect of TFIIF can be blocked by TFIIB. It has been shown that cterRAP74 and the core domain of hTFIIB (TFIIBc, residues 112-316) directly interact with the carboxyl-terminal domain of hFCP1 (cterFCP, residues 879-961), and these interactions may be responsible for the regulatory activities of TFIIF and TFIIB on FCP1. We have determined the NMR solution structure of human cterRAP74, and we have used NMR methods to map the cterFCP-binding sites for both cterRAP74 and human TFIIB. We show that cterFCP binds to a groove of cterRAP74 between alpha-helices H2 and H3, without affecting the secondary structure of cterRAP74. We also show that cterFCP binds to a groove of TFIIBc between alpha-helices D1 and E1 in the first cyclin repeat. We find that the cterFCP-binding site of TFIIBc is very similar to the binding site for the HSV transcriptional activator protein VP16 on the first cyclin repeat of TFIIBc. The cterFCP-binding sites of both RAP74 and TFIIBc form shallow grooves on the protein surface, and they are both rich in hydrophobic and positively charged amino acid residues. These results provide new information about the recognition of acidic-rich activation domains involved in transcriptional regulation, and provide insights into how TFIIF and TFIIB regulate the FCP1 phosphatase activity in vivo.
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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".