Structural Studies of Inositol 1,4,5-Trisphosphate Receptor
Bibliographic record
Abstract
The three isoforms of the inositol 1,4,5-trisphosphate receptor (IP(3)R) exhibit distinct IP(3) sensitivities and cooperativities in calcium (Ca(2+)) channel function. The determinants underlying this isoform-specific channel gating mechanism have been localized to the N-terminal suppressor region of IP(3)R. We determined the 1.9 Å crystal structure of the suppressor domain from type 3 IP(3)R (IP(3)R3(SUP), amino acids 1-224) and revealed structural features contributing to isoform-specific functionality of IP(3)R by comparing it with our previously determined structure of the type 1 suppressor domain (IP(3)R1(SUP)). The molecular surface known to associate with the ligand binding domain (amino acids 224-604) showed marked differences between IP(3)R3(SUP) and IP(3)R1(SUP). Our NMR and biochemical studies showed that three spatially clustered residues (Glu-20, Tyr-167, and Ser-217 in IP(3)R1 and Glu-19, Trp-168, and Ser-218 in IP(3)R3) within the N-terminal suppressor domains of IP(3)R1(SUP) and IP(3)R3(SUP) interact directly with their respective C-terminal fragments. Together with the accompanying paper (Yamazaki, H., Chan, J., Ikura, M., Michikawa, T., and Mikoshiba, K. (2010) J. Biol. Chem. 285, 36081-36091), we demonstrate that the single aromatic residue in this region (Tyr-167 in IP(3)R1 and Trp-168 in IP(3)R3) plays a critical role in the coupling between ligand binding and channel gating.
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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 | 0.000 |
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".