Crystal structure of receptor-binding C-terminal repeats from <i>Clostridium difficile</i> toxin A
Bibliographic record
Abstract
Clostridium difficile is a major nosocomial pathogen that produces two large protein toxins [toxin A (TcdA) and toxin B (TcdB)] capable of disrupting intestinal epithelial cells. Both belong to the family of large clostridial cytotoxins, which are characterized by the presence of a repetitive C-terminal repetitive domain (CRD). In TcdA, the CRD is composed of 39 repeats that are responsible for binding to cell surface carbohydrates. To understand the molecular structural basis of cell binding by the toxins from C. difficile, we have determined a 1.85-A resolution crystal structure of a 127-aa fragment from the C terminus of the toxin A CRD. This structure reveals a beta-solenoid fold containing five repeats, with each repeat consisting of a beta-hairpin followed by a loop of 7-10 residues in short repeats (SRs) or 18 residues in long repeats (LRs). Adjacent pairs of beta-hairpins are related to each other by either 90 degree or 120 degree screw-axis rotational relationships, depending on the nature of the amino acids at key positions in adjacent beta-hairpins. Models of the complete CRDs of toxins A and B suggest that each CRD contains straight stretches of beta-solenoid composed of three to five SRs that are punctuated by kinks introduced by the presence of a single LR. These structural features provide a framework for understanding how large clostridial cytotoxins bind to cell surfaces and suggest approaches for developing novel treatments for C. difficile-associated diseases by blocking the binding of toxins to cell surfaces.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".