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Record W2117563536 · doi:10.1073/pnas.1209018109

Structural asymmetry in the magnesium channel CorA points to sequential allosteric regulation

2012· article· en· W2117563536 on OpenAlexafffund
Roland Pfoh, Angela Li, Nilmadhab Chakrabarti, Jian Payandeh, Régis Pomès, E.F. Pai

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2012
Typearticle
Languageen
FieldNursing
TopicMagnesium in Health and Disease
Canadian institutionsHospital for Sick ChildrenPrincess Margaret Cancer CentreUniversity of TorontoOntario Institute for Cancer Research
FundersCanadian Institutes of Health Research
KeywordsAllosteric regulationBiophysicsDivalentChemistryThermotoga maritimaIntracellularCrystallographyMolecular dynamicsPeriplasmic spaceProtein structureCleavage (geology)Ion channelStereochemistryBiochemistryBiologyGeneComputational chemistryEnzyme

Abstract

fetched live from OpenAlex

Magnesium ions (Mg(2+)) are essential for life, but the mechanisms regulating their transport into and out of cells remain poorly understood. The CorA-Mrs2-Alr1 superfamily of Mg(2+) channels represents the most prevalent group of proteins enabling Mg(2+) ions to cross membranes. Thermotoga maritima CorA (TmCorA) is the only member of this protein family whose complete 3D fold is known. Here, we report the crystal structure of a mutant in the presence and absence of divalent ions and compare it with previous divalent ion-bound TmCorA structures. With Mg(2+) present, this structure shows binding of a hydrated Mg(2+) ion to the periplasmic Gly-Met-Asn (GMN) motif, revealing clues of ion selectivity in this unique channel family. In the absence of Mg(2+), TmCorA displays an unexpected asymmetric conformation caused by radial and lateral tilts of protomers that leads to bending of the central, pore-lining helix. Molecular dynamics simulations support these movements, including a bell-like deflection. Mass spectrometric analysis confirms that major proteolytic cleavage occurs within a region that is selectively exposed by such a bell-like bending motion. Our results point to a sequential allosteric model of regulation, where intracellular Mg(2+) binding locks TmCorA in a symmetric, transport-incompetent conformation and loss of intracellular Mg(2+) causes an asymmetric, potentially influx-competent conformation of the channel.

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)0.002
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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.377
Threshold uncertainty score0.214

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0010.000
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 head0.065
GPT teacher head0.345
Teacher spread0.280 · 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 designObservational
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

Citations76
Published2012
Admission routes2
Has abstractyes

Explore more

Same venueProceedings of the National Academy of SciencesSame topicMagnesium in Health and DiseaseFrench-language works237,207