Sequence Analysis of P4-ATPases Reveals the Structural Determinants for the Stable Monomeric P4B-ATPase Phospholipid Transporters
Bibliographic record
Abstract
ABSTRACT The P4-ATPase family of phospholipid flippases plays a critical role in the maintenance of membrane asymmetry and consequently, various roles in cellular protein traffic and eukaryotic homeostasis. Currently, several structures of these (usually heterodimeric) phospholipid flippases have been resolved, along with extensive biochemical characterization of the substrate transport properties. However, an essential subfamily of monomeric phospholipid flippases, the P4B-ATPases, remains to be characterized in depth. While these P4B-ATPases appear to have similar lipid transport properties to their heterodimeric counterparts, the P4A-ATPases, the basis of their existence as monomers is currently unknown. In addition, the unique features of this group have yet to be comprehensively analyzed since the resolution of one P4B-ATPase member. In this study, we investigated the divergence of P4B-ATPases from other P-type ATPases using a structure-based sequence analysis approach. This led to identification of features unique to P4B-ATPases, as well as previously unidentified conserved properties of P4-ATPases. The results of this study provide a basis for further studies on P4-ATPases to characterize conserved properties of this group that supersedes substrate specificities. MANUSCRIPT INFORMATION - Number of manuscript pages: 20 (double-spaced). - Number of Figures: 5. - Number of Tables: 3. - Supplementary materials include 2 supplementary tables.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".