Symmetric stimulation of Hsp90 catalyzed ATP hydrolysis through enhanced active site gate dynamics
Bibliographic record
Abstract
Heat shock protein 90 (Hsp90) is a vital molecular chaperone that is essential for activating a diverse array of regulatory proteins through an ATP-dependent clamping cycle. The Hsp90 clamping cycle is driven by large-amplitude conformational changes within the N-terminal ATPase domain, including the release of an autoinhibitory N-terminal β-strap followed by a less well-characterized ATP gate rearrangement involving N-terminal helix 1. Here, we employed a combination of 19 F nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics (MD) simulations, and ATPase assays to examine the effects of targeted β-strap and helix 1 mutations. Our findings reveal that targeted disruption of helix 1 packing against the ATPase domain accelerates clamp closure, symmetrically enhancing ATP hydrolysis for both subunits of the Hsp90 dimer, whereas activation by the Aha1 cochaperone is disrupted. Decreasing the energy barrier associated with helix 1 release is a key step in modulating the energy landscape that governs the dynamics of the Hsp90 clamping cycle.
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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 | 0.000 |
| 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".