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Record W4412593801 · doi:10.1002/pro.70231

Structural investigations connect the disordered N‐terminal extension of <scp>HypB</scp> to the activities of <scp>HypB</scp> and <scp>SlyD</scp> in <i>E. coli</i>

2025· article· en· W4412593801 on OpenAlexafffund
Wayne Wing Him Law, Dmitry Pichugin, Ranjith Muhandiram, Deborah B. Zamble, Voula Kanelis

Bibliographic record

VenueProtein Science · 2025
Typearticle
Languageen
FieldEnergy
TopicMetalloenzymes and iron-sulfur proteins
Canadian institutionsUniversity of Toronto
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsChemistryCrystallographyStereochemistryBinding siteNucleotideBiochemistryGene

Abstract

fetched live from OpenAlex

The activities of [NiFe]-hydrogenase enzymes, which are critical to many microbes, require insertion of a Ni(II) ion into the bimetallic catalytic center. Delivery of Ni(II) to [NiFe]-hydrogenases depends, in part, on the metallochaperone HypB, which lies at the center of a Ni(II) transfer pathway that includes the metal storage protein SlyD and the metallochaperone HypA. SlyD is a source of Ni(II) ions for HypB, whereas Ni(II) from HypB is transferred to HypA. In this work, we examine how the intrinsically disordered N-terminal extension (NTE) of HypB modulates the action of the HypB GTPase domain (G-domain). The NTE contains a high-affinity Ni(II) binding site, while the G-domain contains a lower affinity Ni(II) binding site that is affected by binding of guanine nucleotides. The HypB G-domain is also affected by SlyD and provides Ni(II) to HypA. Our NMR data show that, although disordered, the HypB NTE possesses residual structure and makes transient interactions with the HypB G-domain and with SlyD. A set of common residues in the center of the NTE are affected by SlyD and G-domain binding, and also by binding of Ni(II) to the high-affinity site located at the N terminus of the protein. The NTE interacts with residues in or near the Ni(II)- and GDP-binding sites in the G-domain, which are also affected when SlyD binds the NTE. Thus, the data showcase a complex interaction network between HypB and SlyD, and provide molecular details regarding how the HypB NTE links the activities of the HypB G-domain and SlyD.

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)0.006
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
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 score0.082
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.006
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.003
Science and technology studies0.0010.003
Scholarly communication0.0000.001
Open science0.0010.001
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 head0.018
GPT teacher head0.255
Teacher spread0.237 · 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.

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
Published2025
Admission routes2
Has abstractyes

Explore more

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