Chdi Conference 2017 Poster: Pursuit Of A High Resolution Structure Of Full-Length Huntingtin By Cryo-Electron Microscopy
Bibliographic record
Abstract
Huntington’s disease is hallmarked by the CAG expansion of the huntingtin gene. How the corresponding polyQ expansion affects the structure of the encoded huntingtin protein remains poorly understood in the absence of a high resolution full-length protein structure. Huntingtin is a large, monomeric protein of 350 kDa, an ideal size for electron microscopy based structural biology methods. Using protein derived from a baculovirus expression system, we have successfully calculated a new protein envelope of huntingtin at ~15 Å resolution by negative stain electron microscopy. This reveals a claw-shaped molecule with a large central cavity. Grids of the protein sample have been optimized to produce a disperse array of homogenous protein particles in a fine vitreous ice layer for analysis by cryo-electron microscopy. A high resolution dataset has been collected on a Krios instrument and work is continuing in pursuit of this protein structure. This project is part of the open notebook labscribbles, through which methods and data are freely shared through the repository Zenodo under a CC-by license in real time in an effort to catalyse research in this area.
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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 | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.005 | 0.002 |
| Open science | 0.002 | 0.005 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.174 | 0.109 |
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".