Heat-Induced Dimerization of BCL-x<sub>L</sub> through α-Helix Swapping
Bibliographic record
Abstract
The dimerization of anti-apoptotic BCL-xL by three-dimensional domain swapping has recently been discovered at alkaline pH; however, the high energetic barrier between the dimer and monomer forms of BCL-xL prevents them from interconverting at room temperature and neutral pH. Here, we demonstrate that BCL-xL dimers can be easily prepared by heating concentrated protein above 50 degrees C. The 38 kDa BCL-xL dimer was fully characterized by multi-resonance nuclear magnetic resonance (NMR) spectroscopy, and the mechanism of dimerization by alpha-helix swapping was confirmed. Dimerization strongly affects the NMR signals from the turn between helices alpha5 and alpha6 of BCL-xL and a portion of the long loop between helices alpha1 and alpha2. Measurements of residual dipolar couplings demonstrate that the solution structure of the BCL-xL dimer is very close to the crystal structure. Dimer formation does not prevent tight binding of ligands to the hydrophobic cleft of BCL-xL; however, binding of a BID BH3-peptide or a polyphenol drug, gossypol, to BCL-xL significantly slowed monomer-dimer interconversion and is an example of the control of BCL protein oligomerization by ligand binding.
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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".