Bibliographic record
Abstract
Equine gelsolin, a protein involved in regulating linear actin assembly, has been analyzed at various hierarchical levels of protein organization. At the genetic level, the coding message for the intracellular cytoplasmic form of gelsolin consists of 2196 nucleotide bases, which translates into a 731 amino acid protein with a molecular mass of 80 696 daltons. The amino acid sequence derived from the cloned DNA for the equine protein shares 94.7% identity with that of cytoplasmic human gelsolin. The exon that codes for the stretch of amino acids found at the N-terminus of horse cytoplasmic gelsolin is identical in size (206 nucleotides) and similar in composition to human gelsolin exon 4. The form of horse gelsolin that is secreted into blood plasma is distinguished from the cytoplasmic protein by an extension of 25 amino acids at the N-terminus. Spectroscopic examination of the solution structure of the Ca²⁺-free form of horse plasma gelsolin estimates the a-helix and (3-sheet contents at 16% and 23%, respectively. Similar analysis with Ca²⁺-bound gelsolin yields an ⍺-helix content of 17% and 22% β-structure. The predicted conformational weights of Ca²⁺-free gelsolin agree favorably with values derived from the crystal structure of the protein, which shows 18% ⍺-helix and 23% β-structure. Monitoring the loss of these secondary structural elements during the course of unfolding experiments reveals that the behaviors of both native and chemically modified horse plasma gelsolin towards chemical denaturants depend greatly on the surface charge of the protein. Interaction with Ca²⁺ and guanidinium cations alters the charge on gelsolin's surface, which not only affects protein structure, but modifies the pathway of unfolding. The path to the denatured state does not follow a simple two-state cooperative mechanism, but likely passes through various intermediate conformations which reflect the multi-domain configuration of gelsolin. Whole horse plasma gelsolin purified in the course of this project was used to grow crystals suitable for x-ray diffraction analysis. The 3-dimensional structure (Burtnick, L.D., Robinson, R.C., and Koepf, E.K., 1996, Biophysical Journal, 70, A14), which confirms the existence of six similar domains, S1-S6, was solved in the absence of bound Ca²⁺. Superposition of Ca²⁺-free horse SI onto Ca²⁺-bound human SI produces an almost exact overlay, suggesting that Ca²⁺ does not exert its regulatory activity on gelsolin by altering the folding within an individual domain in a significant way. Modeling studies with gelsolin and F-actin provide a means of relating the structure of whole gelsolin to its biological activities. Docking of whole horse gelsolin with a model for the human SI-F-actin complex demonstrates how both capping and nucleating activities may come about, but does not adequately explain either the severing function or why Ca²⁺-free gelsolin does not bind to F-actin. A model in which Ca²⁺ binding induces shifts in the relative positions of the six domains would seem to be required.
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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 | 0.000 |
| 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".