O16.4 Structural similarity of<i>treponema pallidum</i>protein Tp0225 with human toll-like receptor 2
Bibliographic record
Abstract
Background The causative agent of syphilis, Treponema pallidum, is a highly invasive chronic pathogen. Here we used bioinformatics and structural biology to characterize the sole LRR-containing protein in T. pallidum, Tp0225. In other bacterial pathogens, Leucine-Rich Repeat (LRR)-containing proteins contribute to chronicity by mediating attachment, invasion and immune evasion. Methods A phylogenetic tree was constructed to determine the evolutionary relationship between Tp0225 and LRR homologs from pathogenic and non-pathogenic treponemes. The size and organization of Tp0225 protein domains were analyzed by comparing them to the domains of the treponemal homologs. For structure determination, the full-length recombinant protein was purified, crystallized, and the three dimensional structure determined using X-ray crystallography. Results Bioinformatic analyses showed that Tp0225 has diverged more from non-pathogens compared to pathogens during evolution. The structure of Tp0225 demonstrated that the protein adopts a non-classical LRR fold and contains a hydrophobic pocket on the surface of the structure. This unusual LRR characteristic is similar to the hydrophobic pocket found on the surface of the human Toll-like Receptor 2 (TLR2) LRR domain that recognizes T. pallidum during infection. Conclusion We have determined the structure of the only LRR-containing protein in T. pallidum and have shown that it contains an unusual LRR structural feature that is shared with the host innate immune signaling molecule TLR2. This structural mimicry may be involved in subversion of normal host processes during T. pallidum infection. Disclosure No significant relationships.
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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) | 0.005 | 0.001 |
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".