Cholesterol sensitivity of KIR2.1 depends on functional inter-links between the N and C termini
Bibliographic record
Abstract
In recent years, cholesterol has been emerging as a major regulator of ion channel function. We have previously shown that cholesterol suppresses Kir2 channels, a subfamily of constitutively active strongly rectifying K (+) channels. Furthermore, our earlier studies have shown that cholesterol sensitivity of Kir2 channels depends on a group of residues that form a belt-like structure around the cytosolic pore of the channel in proximity to the transmembrane domain. In this study, we focus on the contributions of different structural domains of Kir2 channels in the regulation of their cholesterol sensitivity. Focusing on the mildest mutation in the sensitivity belt, L222I, we show that the sensitivity of the channel to cholesterol can be restored by crosstalk between three distinct cytosolic regions: the C-terminal CD loop, the EF and GA loops of the C-terminus, and the βA sheet of the N-terminus. Thus, in addition to the importance of residues that affect the cytosolic G-loop gate in the sensitivity of Kir2 channels to cholesterol, our data suggest an important role to the interactions at the interface between the channel's N- and C- termini that couple the intracellular domains of its four subunits during 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 | 0.000 |
| 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".