Structural insights into the cytoplasmic domain of a human BK channel
Bibliographic record
Abstract
The large conductance, voltage- and Ca2+-activated K+ (BK or Slo1) channel is widely expressed in mammalian cells/tissues (i.e. neurons, skeletal and smooth muscles, exocrine cells, the inner ear) and regulates action potential firing, muscle contraction and secretion. The large ionic conductance and unusual, dual stimulus-driven gating behavior of this channel have long intrigued membrane biophysicists, and recent structure/function analyses have provided increasingly detailed insights into the molecular “bells and whistles” that regulate BK channel activity. Now, in two complementary articles published by the groups of Rod MacKinnon and Youxing Jiang, high resolution x-ray crystal structures of the human BK channel’s large cytoplasmic domain have been solved in both the absence and presence of bound Ca2+, conditions which would presumably promote the resting and activated conformations of this large domain. Given the regulatory importance of the cytosolic domain on BK channel gating, these experimentally determined structures reveal a number of key insights, including: 1) the physical arrangement and interactions of the tandem RCK1 and RCK2 domains within a single channel subunit, 2) the assembly of the four large cytoplasmic domains into a symmetric, tetrameric complex, 3) the formation of the channel’s “gating ring” structure, based on the assembly of the individual RCK1 and 2 domains, and 4) the structural elements underlying the regions critical for divalent metal ion binding (i.e. Ca2+ and Mg2+) and their potential influence on conduction pore opening. Commentary to: Yuan P, Leonetti MD, Pico AR, Hsiung Y, MacKinnon R. Structure of the human BK channel Ca2+-activation apparatus at 3.0 Å resolution. Science 2010; 329:182–6; PMID: 20508092; DOI: 10.1126/science.1190414; and Wu Y, Yang Y, Ye S, Jiang Y. Structure of the gating ring from the human large-conductance Ca2+-gated K+ channel. Nature 466: 393-397; PMID: 20574420; DOI: 10.1038/nature09252
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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 | 0.000 |
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".