Analysis of co‐chaperone interactions with Hsp90 (567.7)
Bibliographic record
Abstract
Heat shock protein 90 (Hsp90) is a highly abundant, ATP‐dependent molecular chaperone that is present in all eukaryotic cells. It is essential for the maturation and regulation of a specific set of substrate (client) proteins, many of which are key players in oncogenesis. Hsp90, as a homodimer, acts in the context of a complicated ATPase cycle. Co‐chaperone proteins guide and modulate Hsp90 through its functional cycle in order to mature clients, by binding to one or more of Hsp90’s domains in a sequential manner. To address Hsp90’s conformational requirements for cycle progression, we analyze two specific co‐chaperones, Aha1 and Sba1, which bind to Hsp90 in its closed, ATP‐bound state. We have constructed 14 Hsp90 variants harboring mutations in the N terminus of Hsp90 which have the potential to block the binding of Aha1 and Sba1. Several N‐terminal mutants show promising results as they are weakly stimulated by Aha1 or cannot be inhibited by Sba1 from the Aha1‐stimulated rate. Interestingly, one specific mutant harboring the D132K mutation does not interact with Sba1. Analysis of these five mutants in combination with previously characterized Hsp90 mutants will allow for the restriction of either Sba1 or Aha1 to one monomer of Hsp90 or the other. This subunit complementation strategy will bring insight into how Aha1 and Sba1 act asymmetrically on Hsp90. Grant Funding Source : Supported by CIHR
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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".