Structural determination of the phosphorylation domain of the ryanodine receptor
Bibliographic record
Abstract
The ryanodine receptor ( R y R ) is a large, homotetrameric sarcoplasmic reticulum membrane protein that is essential for C a 2+ cycling in both skeletal and cardiac muscle. Genetic mutations in R y R 1 are associated with severe conditions including malignant hyperthermia ( MH ) and central core disease. One phosphorylation site ( S er 2843) has been identified in a segment of R y R 1 flanked by two R y R motifs, which are found exclusively in all R y R isoforms as closely associated tandem (or paired) motifs, and are named after the protein itself. These motifs also contain six known MH mutations. In this study, we designed, expressed and purified the tandem R y R motifs, and show that this domain contains a putative binding site for the C a 2+ /calmodulin‐dependent protein kinase β isoform. We present a 2.2 Å resolution crystal structure of the R y R domain revealing a two‐fold, symmetric, extended four‐helix bundle stabilized by a β sheet. Using mathematical modelling, we fit our crystal structure within a tetrameric electron microscopy (EM) structure of native R y R 1, and propose that this domain is localized in the R y R clamp region, which is absent in its cousin protein inositol 1,4,5‐trisphosphate receptor. Database The crystal structure of the RyR1 phosphorylation domain (amino acid residues 2734–2940) has been submitted to the Protein Data Bank under accession number 3RQR . Structured digital abstract RyR1 C3 physically interacts with CaMKIIβ by pull down ( View interaction ) RyR1 C3 binds to CaMKIIβ by pull down ( View interaction ) CaMKIIβ physically interacts with RyR1 C3 by anti tag coimmunoprecipitation (View Interaction: 1 , 2 )
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".