Atomic Resolution Interactions Regulating Partitioning of a FUS Folded RRM Domain into Model CAPRIN1 Condensates
Bibliographic record
Abstract
Biomolecular condensates enrich specific client molecules while excluding others, often modulating conformational landscapes, and hence functions, of molecules dissolved within them. NMR-based atomic resolution studies have focused on interactions between scaffold proteins and the unfolded states of client proteins to understand the factors that influence client partitioning into condensed phases. However, characterization of interactions involving the folded client conformer is required to obtain a complete picture of how dissolution within the condensed phase affects the client energy landscape. Here, we use solution NMR spectroscopy to investigate, at atomic resolution, the interactions mediating the selective partitioning of a folded client, the FUS RNA Recognition Motif (RRM), into condensates formed by the scaffold protein CAPRIN1. At 40 °C, approximately 40% of FUS RRM remains folded in the CAPRIN1 condensed phase and high-resolution [ 1 H– 15 N]-HSQC spectra can be recorded, enabling site-specific interactions between the folded client and scaffold to be mapped across the entire FUS RRM sequence. Using intermolecular NOE and PRE (mixed solutions), and chemical shift perturbation (demixed solution) analyses, we identify a set of interaction surfaces on the folded FUS RRM that enable multiple contacts with aromatic- and arginine-rich regions of CAPRIN1. These heterotypic interactions lead to a 30-fold enrichment of FUS RRM within the condensate and overlap with sites responsible for CAPRIN1 homotypic phase separation, suggesting a shared molecular basis for scaffold-scaffold and scaffold-client recognition. Notably, tyrosine phosphorylation of CAPRIN1 disrupts these interactions and reduces client partitioning by over 2 orders of magnitude, highlighting how post-translational modifications can profoundly regulate condensate composition.
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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 | 0.000 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".