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Record W4407104071 · doi:10.1038/s41467-025-56491-9

Structural insights into light-gating of potassium-selective channelrhodopsin

2025· article· en· W4407104071 on OpenAlexafffund
Takefumi Morizumi, Kyumhyuk Kim, Hai Li, Probal Nag, Tal Dogon, Oleg A. Sineshchekov, Yumei Wang, Leonid S. Brown, Songhwan Hwang, Han Sun, Ana‐Nicoleta Bondar, Igor Schapiro, Elena G. Govorunova, John L. Spudich, Oliver P. Ernst

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldNeuroscience
TopicPhotoreceptor and optogenetics research
Canadian institutionsUniversity of GuelphUniversity of Toronto
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchIsrael Science FoundationForschungszentrum JülichNational Institutes of HealthU.S. Department of Health and Human ServicesGovernment of CanadaNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesUniversity of Texas Health Science Center at HoustonDeutsche Forschungsgemeinschaft
KeywordsChannelrhodopsinGatingOptogeneticsPotassium channelPotassiumChemistryBiophysicsNeuroscienceBiology

Abstract

fetched live from OpenAlex

Structural information on channelrhodopsins’ mechanism of light-gated ion conductance is scarce, limiting its engineering as optogenetic tools. Here, we use single-particle cryo-electron microscopy of peptidisc-incorporated protein samples to determine the structures of the slow-cycling mutant C110A of kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) in the dark and upon laser flash excitation. Upon photoisomerization of the retinal chromophore, the retinylidene Schiff base NH-bond reorients from the extracellular to the cytoplasmic side. This switch triggers a series of side chain reorientations and merges intramolecular cavities into a transmembrane K+ conduction pathway. Molecular dynamics simulations confirm K+ flux through the illuminated state but not through the resting state. The overall displacement between the closed and the open structure is small, involving mainly side chain rearrangements. Asp105 and Asp116 play a key role in K+ conductance. Structure-guided mutagenesis and patch-clamp analysis reveal the roles of the pathway-forming residues in channel gating and selectivity. Channelrhodopsins’ mechanism of light-gated ion conductance could be engineered for use in optogenetic tools. Here, structures of the slow-cycling mutant of HcKCR1, including an open state structure, provide insight into channel gating and selectivity.

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)0.001
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 score0.095
Threshold uncertainty score0.443

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0020.001
Research integrity0.0000.001
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 head0.038
GPT teacher head0.370
Teacher spread0.332 · 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

Citations8
Published2025
Admission routes2
Has abstractyes

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