Structural characterization of the <i>Helicobacter pylori</i> peptidyl-prolyl <i>cis</i>,<i>trans</i>-isomerase HP0175 reveals an extension of chaperone helices upon target interaction
Bibliographic record
Abstract
Within a host, pathogenic bacteria employ several mechanisms that enhance their survival and motility. Helicobacter pylori secretes several virulence factors, including VacA, CagA, -glutamyltrasnpeptidase and HP0175. The secreted HP0175 has been shown to induce cell apoptosis through a cascade of mechanisms initiated through binding to Toll Like Receptor 4 (TLR4). HP0175 is classified as a parvulin-like peptidylprolyl cis,trans-isomerase (PPIase) involved in the isomerization of proline-containing peptide bonds. We have crystallized apo-HP0175 and determined the structure to 2.09 resolution. A comparison to the indole-2-carboxylic acid bound HP0175 form of the protein reveals that the N-and C-terminal helices of the chaperone domain extend upon engagement of the catalytic residues in the binding pocket by the inhibitor. Further, chromatographic and mass spectrometric analysis of HP0175 reveals that dimerization of the active form of the protein is dependent on ionic strength. These structural observations support the finding in other parvulins that the N-and C-terminal helices stabilize proteins undergoing catalysis by the PPIase domain, as well as suggest a means by which HP0175 could bind to TLR4, thereby initiating an apoptotic cascade in infected cells.
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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".