Trivalent anions as probes of the CFTR channel pore
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Bibliographic record
Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) Cl -channel uses positively charged amino-acid side-chains to form binding sites for permeating anions.These binding sites have been investigated experimentally using a number of anionic probes.Mutations that alter the distribution of positive and negative charges within the pore have differential effects on the binding of monovalent versus divalent anions.This study uses patch clamp recording from wild-type and pore-mutant forms of CFTR to investigate small trivalent anions (Co(NO 2 ) 6 3-, Co(CN) 63-and IrCl 6 3-) as potential probes of anion binding sites.These anions caused weak block of Cl -permeation in wild-type CFTR (Kd 700 M) when applied to the intracellular side of the membrane.Mutations that increase the density of positive charge within the pore (E92Q, I344K, S1141K) increased the binding affinity of these anions 80-280-fold, and also greatly increased the voltage-dependence of block, consistent with fixed charges in the pore affecting monovalent : multivalent anion selectivity.However, high-affinity pore block by Co(NO 2 ) 6 3-apparently did not alter channel gating, a hallmark of high-affinity binding of divalent Pt(NO 2 ) 4 2-ions within the pore.This work increases the arsenal of probes available to investigate anion binding sites within Cl -channel pores.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 it