New insights into the folding–unfolding mechanism and conformations of cytochrome C
Bibliographic record
Abstract
Metalloproteins account for over one-third of all proteins in nature and play important roles in biological processes. The formation of the native structures of metalloproteins requires not only the correct folding of the polypeptide chains but also the proper incorporation of metal cofactors. Understanding the folding mechanism of metalloproteins has been challenging. Horse heart cytochrome C (cytc) is a classical model system for protein folding studies. Although a large number of ensemble studies have been carried out to characterize the folding mechanism of cytc, there is still a significant debate on the folding mechanism and the existence of the proposed "foldons". Here, we used single-molecule optical tweezers to probe the mechanical folding-unfolding behaviors of cytc at the single-molecule level. By directly monitoring the folding and unfolding of holo-cytc, we revealed novel insights into the folding of cytc. Our results showed that the structural elements that are distant from the N- and C-termini can exist as a short-lived intermediate, a finding that contrasts with the general belief that the folding and packing of the N- and C-terminal helices are prerequisites for the folding of other structural elements in cytc. In addition, our results present strong evidence that apo-cytc, which has been long believed to be a random coil, is not a true random coil, and weak interactions within the unfolded polypeptide chain exist. Our results bring new insights into our understanding of the folding mechanisms of heme proteins as well as the role of heme in the folding process.
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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 | 0.000 | 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".