Demixing of four simultaneously co-expressed phase-separating proteins in the endoplasmic reticulum lumen
Why this work is in the frame
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Bibliographic record
Abstract
Intracellular protein crystallization represents an intriguing form of biomolecular assembly. While the list of intracellularly crystallizing proteins is growing and their physiological roles are being elucidated, the underlying requirements and processes for intracellular crystallogenesis remain largely unknown. To reveal cellular capacity and morphological plasticity to accommodate protein crystals and crystal-like inclusion bodies, this study examines how simultaneously co-expressed phase-separating proteins influence each other's behavior in the endoplasmic reticulum (ER) lumen. To this end, four cargoes were selected based on their ability to produce distinctive inclusion body types and morphologies irrespective of originating species, function, or sequence homology. The co-expressed model proteins independently phase-separated into distinctive inclusions and coexisted in the ER without losing their signature morphologic characteristics. The continued growth of intra-ER protein crystals and droplets suggested that co-expressed cargo proteins were continuously synthesized and folded in the ER, thereby fueling the growth of the corresponding inclusion bodies. Thus, even in the crowded ER environment, each of the four overexpressed cargo proteins can find their mates through self-association and assemble into four unique structures in the ER. This study demonstrates that cells can accommodate up to four distinct types of mesoscale inclusion bodies in the ER lumen simultaneously, and the respective phase-separation events proceed without interfering with each other and without morphological mixing.
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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 | 0.001 | 0.001 |
| 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) | 0.000 | 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