Conformational Change in the Vinculin C-terminal Depends on a Critical Histidine Residue (His-906)
Bibliographic record
Abstract
A phospholipid-controlled interaction between the N-terminal and C-terminal domains of vinculin is thought to be a major mechanism that regulates binding activities of the protein. To probe the mechanisms underlying these interactions we used chemical modification and site-directed mutagenesis directed at histidine residues. Diethylpyrocarbonate (DEPC) modification of the C-terminal, but not the N-terminal, domain greatly decreased affinity of the N-terminal-C-terminal binding, implicating histidine residues in the C-terminal. Mutation of either or both C-terminal histidines (at positions 906 and 1026), however, did not affect N-C binding at neutral pH. The H906A mutation did prevent DEPC effects and also prevented the normal decrease in binding affinity for the N-terminal at lower pH. We found that the wild type C-terminal domain, but not the H906A mutant, underwent a conformational change at pH 6.5, reflected in an altered circular dichroism spectrum and apparent oligomerization. Phospholipid also induced conformational changes in the wild type C-terminal domain but not in the H906A mutant, even though the mutant protein did bind to the phospholipid. Finally, the sensitivity of the N-C interaction to phospholipid was much reduced by the H906A mutation. These results show that H906 plays a key role in the conformational dynamics of the C-terminal domain and thus the regulation of vinculin.
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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".