Bibliographic record
Abstract
Most of us who teach protein structure have very likely stood in front of a class at some point and confidently stated that any two naturally occurring proteins displaying 40% sequence identity will be homologous and thus possess the same fold. A paper by Roessler et al. (1) in a recent issue of PNAS has definitively overturned this basic tenet by demonstrating that a pair of protein homologues displaying 40% identity exhibit markedly different folds. These proteins are both repressors of the Cro family and were identified in prophage sequences present in the genomes of the bacterial species, Pseudomonas fluorescens (Pfl 6) and Xylella fastidiosa (Xfaso 1). The atomic resolution structures of these proteins, solved by Roessler et al. using x-ray crystallography, reveal a similar N-terminal helix–turn–helix but widely diverging C-terminal regions; Xfaso 1 displays an all-helical monomeric fold, whereas the Pfl 6 C terminus forms an intertwined β-sheet dimer (Fig. 1 A). The conclusion that these proteins are descended from a common ancestor is strongly supported. An alignment of homologues of each of these protein shows that many positions are conserved across both groups of proteins even in the C-terminal region where the structures diverge (Fig. 1 B). This conservation pattern argues against a distinct C terminus being placed onto one of these proteins through a nonhomologous recombination event. The genomic context of the genes encoding these proteins with respect to other surrounding phage genes is also highly conserved, which implies a common ancestry and function.
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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 | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.003 | 0.003 |
| Scholarly communication | 0.004 | 0.007 |
| Open science | 0.001 | 0.006 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.073 | 0.024 |
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".