A Low Affinity Cavb4a/Rem2 Interaction is Required for Inhibition of Cav2.1 Ca2+ Currents
Bibliographic record
Abstract
RGK (Rem, Rad, Kir/Gem proteins) proteins, including Rem2, cause profound inhibition of high‐voltage activated Ca 2+ channels containing intracellular regulatory b subunits. All RGK proteins bind to Cavb subunits in vitro, but the necessity of the interaction for current inhibition remains controversial. This study applies solution state nuclear magnetic resonance (NMR) and calorimetric techniques to map the binding site for Rem2 on human Cavb4a and to measure the binding affinity. Our experiments revealed two binding surfaces on the b4 GK domain contributing to a 156 μM Kd interaction: 1) a hydrophobic pocket surrounded by four residues, mutation of any of which completely disrupted binding; and 2) a nearby surface containing three residues that when individually mutated decreased affinity. Cav2.1 Ca 2+ currents were completely inhibited by Rem2 when co‐expressed with wild‐type Cavb4a, but were unaffected by Rem2 when co‐expressed with a Cavb4a site 1 mutant. These results provide direct evidence for a low affinity Rem2/Cavb4 interaction and its essential role in Cav2.1 inhibition by Rem2.
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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) | 0.002 | 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".