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Record W7116744721 · doi:10.1038/s41467-025-67144-2

Structural insights into AQP3 channel closure upon pH and redox changes reveal an autoregulatory molecular mechanism

2025· article· en· W7116744721 on OpenAlexafffund
Raminta Venskutonytė, Carter J. Wilson, Sara Bsharat, Rashmi B. Prasad, Pontus Gourdon, Isabella Artner, Bert L. de Groot, Lindkvist-Petersson Karin

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicIon Transport and Channel Regulation
Canadian institutionsEngineering Link (Canada)
FundersStockholms UniversitetScience for Life LaboratoryUmeå UniversitetLunds UniversitetDiabetesfondenKempestiftelsernaChina Scholarship CouncilCancerfondenVetenskapsrådetNatural Sciences and Engineering Research Council of CanadaKempe Foundation
KeywordsExtracellularAquaporinRedoxIntracellularAquaporin 3Hydrogen peroxideReactive oxygen speciesHomeostasis

Abstract

fetched live from OpenAlex

Abstract Regulation of intracellular levels of reactive oxygen species (ROS) remains poorly understood. Aquaporin 3 (AQP3) facilitates the membrane transport of hydrogen peroxide (H 2 O 2 ), a key ROS signaling molecule. Here we elucidate the molecular mechanism of AQP3 and show that its regulatory properties are both pH dependent and autoregulated by H 2 O 2 . Using single particle cryo-electron microscopy, we present open and closed conformations of human AQP3. At pH 8.0, the channel adopts an open state, while acidic pH or exposure to H 2 O 2 promotes closure via a large conformational rearrangement of extracellular loop E. These findings reveal a mechanism for autoregulation of H 2 O 2 transport and establish AQP3 as a key modulator of redox homeostasis in human pancreatic β-cells.

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 score0.113
Threshold uncertainty score0.746

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 science0.0010.000
Research integrity0.0010.000
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 head0.008
GPT teacher head0.264
Teacher spread0.257 · 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

Citations1
Published2025
Admission routes2
Has abstractyes

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