A TATA-box-binding protein binds single-stranded DNA in two modes: To poly(G) tracts and to flexible DNA regions
Bibliographic record
Abstract
The TATA-box-binding protein (TBP) homolog from Giardia intestinalis (gTBP) is highly divergent, lacking key phenylalanine residues crucial for binding and unwinding double-stranded DNA. Surprisingly, we determined that gTBP exhibits unconventional DNA-binding properties and preferentially binds to single-stranded DNA (ssDNA) using a DNA-binding pocket that is narrower relative to other eukaryotic TBPs. Additionally, we showed that gTBP binds in two distinct modes, which we call the A and B modes, that are dependent on ssDNA sequence and protein concentration. For the A mode, gTBP binds as an oligomer to ssDNA that contains four or more consecutive guanine bases. For the B mode, using base stacking energy potentials between adjacent dinucleotides as a simple proxy for per-nucleotide flexibility, gTBP binds as a monomer to ssDNA in a manner that is dependent on DNA structural properties. To validate the latter concept, we designed de novo DNA sequences with base stacking energy profiles comparable to two DNA sequences that bind gTBP and showed that these designed sequences can compete for gTBP binding against the two original sequences. Overall, we present a potential new perspective on eukaryotic transcription regulation based on our findings around unconventional gTBP-ssDNA binding. A comprehensive understanding of the binding modes of gTBP could yield insights into Giardia's biology and eukaryotic transcription in general.
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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 | 0.001 |
| 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".