Effects of Zinc Binding on the Structure and Dynamics of the Intrinsically Disordered Protein Prothymosin α: Evidence for Metalation as an Entropic Switch
Bibliographic record
Abstract
Prothymosin alpha (ProTalpha) is a small acidic protein that is highly conserved among mammals. The human form has 110 amino acid residues (M.W. 12.1 kDa; pI approximately 3.5) and is found to be expressed in a wide variety of tissues. ProTalpha plays an essential role in cell proliferation and apoptosis, and it is involved in transcriptional regulation of oxidative stress-protecting genes. Despite the multiple biological functions ProTalpha has, the protein does not adopt a well-defined three-dimensional structure under physiological conditions. Previous studies have shown that the interaction between ProTalpha and some of its protein targets is significantly enhanced in the presence of zinc ions, suggesting that zinc binding plays a crucial role in the protein's function. In this work, we use nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry to characterize the structure and dynamics of ProTalpha and its complexation with Zn2+. We found that zinc binding causes partial folding of the C-terminal half of ProTalpha, especially the Glu-rich region, while the N-terminal portion of the protein remains largely unstructured. The metalated protein also exhibits a significantly reduced flexibility. ProTalpha shows a high specificity for Zn2+, and the interactions with other divalent cations (Ca2+, Mg2+) are much weaker. On the basis of the site-specific information obtained here, as well as the results from previous studies, we propose that the conformational and dynamic changes upon zinc binding may act as an entropic switch that greatly facilitates the binding to other proteins.
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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 | 0.001 |
| 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".