Collaboration between two conserved sequence motifs drives <scp>ATPase</scp> stimulation of Hsp90 by Aha1
Bibliographic record
Abstract
Hsp90 is a dimeric molecular chaperone essential for the folding, stabilization, activation, and maturation of hundreds of client proteins, which are critical for cellular function. Co-chaperones, such as Aha1, play a key role in regulating the ATP-dependent Hsp90 client activation cycle by modulating Hsp90's ATPase activity and controlling progression through the cycle. Two highly conserved motifs in Aha1-the NxNNWHW and RKxK motifs-are known to regulate specific aspects of the Hsp90 ATPase cycle. In this study, we demonstrate that the K60 residue within the RKxK motif facilitates the structural organization of the NxNNWHW motif prior to ATP hydrolysis. Mutation of the K60 residue partially impairs the in vivo functionality of yeast Aha1. Additionally, we reveal that each individual residue within the NxNNWHW motif modulates the ATPase rate and apparent affinity for ATP of Hsp90. These findings provide new insights into how conserved regions of Aha-type co-chaperones influence Hsp90 kinetics and its regulation of client protein folding.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".