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Record W4205748672 · doi:10.1002/1873-3468.14279

The T1‐tetramerisation domain of Kv1.2 rescues expression and preserves function of a truncated NaChBac sodium channel

2022· article· en· W4205748672 on OpenAlexafffund
Nazzareno D’Avanzo, Andrew J. Miles, Andrew M. Powl, Colin G. Nichols, B.A. Wallace, Andrias O. O’Reilly

Bibliographic record

VenueFEBS Letters · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicIon channel regulation and function
Canadian institutionsUniversité de Montréal
FundersNational Heart, Lung, and Blood InstituteMedical Research CouncilEuropean CommissionNatural Sciences and Engineering Research Council of CanadaNational Institutes of HealthCanadian Institutes of Health ResearchBiotechnology and Biological Sciences Research CouncilRosetrees Trust
KeywordsCytoplasmChimera (genetics)MutantSodium channelCell biologyBiophysicsChemistryIon channelTransmembrane domainAlternative splicingBiologyMembraneSodiumMessenger RNABiochemistryGeneReceptor

Abstract

fetched live from OpenAlex

Cytoplasmic domains frequently promote functional assembly of multimeric ion channels. To investigate structural determinants of this process, we generated the ‘T1‐chimera’ construct of the NaChBac sodium channel by truncating its C‐terminal domain and splicing the T1‐tetramerisation domain of the Kv1.2 channel to the N terminus. Purified T1‐chimera channels were tetrameric, conducted Na + when reconstituted into proteoliposomes, and were functionally blocked by the drug mibefradil. Both the T1‐chimera and full‐length NaChBac had comparable expression levels in the membrane, whereas a NaChBac mutant lacking a cytoplasmic domain had greatly reduced membrane expression. Our findings support a model whereby bringing the transmembrane regions into close proximity enables their tetramerisation. This phenomenon is found with other channels, and thus, our findings substantiate this as a common assembly mechanism.

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 distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.091
Threshold uncertainty score0.252

Codex and Gemma teacher scores by category

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 communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.210
Teacher spread0.201 · 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 teacher head, 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
Published2022
Admission routes2
Has abstractyes

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