Structural Insights into the Inactive Subunit of the Apicoplast-localized Caseinolytic Protease Complex of Plasmodium falciparum
Why this work is in the frame
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Bibliographic record
Abstract
The ATP-dependent caseinolytic protease, ClpP, is highly conserved in bacteria and in the organelles of different organisms. In cyanobacteria, plant plastids, and the apicoplast of the genus Plasmodium , a noncatalytic paralog of ClpP, termed ClpR, has been identified. ClpRs are found to form heterocomplexes with ClpP resulting in a ClpRP tetradecameric cylinder having less than 14 catalytic triads. The exact role of ClpR in such a complex remains enigmatic. Here we describe the x-ray crystal structure of ClpR protein heptamer from Plasmodium falciparum ( Pf ClpR). This is the first structure of a ClpR protein. The structure shows that the Pf ClpR monomer adopts a fold similar to that of ClpP, but has a unique motif, which we named the R -motif, forming a β turn located near the inactive catalytic triad in a three-dimensional space. The Pf ClpR heptamer exhibits a more open and flat ring than a ClpP heptamer. Pf ClpR was localized in the P. falciparum apicoplast as is the case of Pf ClpP. However, biochemical and structural data suggest that, contrary to what has been observed in other organisms, Pf ClpP and Pf ClpR do not form a stable heterocomplex in the apicoplast of P. falciparum . Background: In several organisms, caseinolytic proteases have active and inactive subunits termed ClpP and ClpR, respectively. Results: The x-ray structure of ClpR from Plasmodium falciparum ( Pf ClpR) was solved. Conclusion: Pf ClpR monomer has a similar fold as ClpP but the Pf ClpR heptamer exhibits a more open ring than a ClpP heptamer. Significance: This is the first structure of a ClpR subunit.
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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 | 0.001 |
| 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 it