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Record W4396956974 · doi:10.4149/gpb_2024007

Trivalent anions as probes of the CFTR channel pore

2024· article· en· W4396956974 on OpenAlexafffund
Paul Linsdell

Bibliographic record

VenueGeneral Physiology and Biophysics · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicIon channel regulation and function
Canadian institutionsDalhousie University
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsChemistryChannel (broadcasting)Computer scienceTelecommunications

Abstract

fetched live from OpenAlex

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) 6 3-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 μM) 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.009
GPT teacher head0.235
Teacher spread0.226 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2024
Admission routes2
Has abstractyes

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