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Record W3017842490 · doi:10.1101/2020.04.22.056440

Mechanism of NanR gene repression and allosteric induction of bacterial sialic acid metabolism

2020· preprint· en· W3017842490 on OpenAlexaff
Christopher R. Horne, Hariprasad Venugopal, Santosh Panjikar, Amy Henrickson, Emre Brookes, Rachel A. North, James M. Murphy, Rosmarie Friemann, Michael D. W. Griffin, Georg Ramm, Borries Demeler, Renwick C. J. Dobson

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020
Typepreprint
Languageen
FieldEnvironmental Science
TopicBacteriophages and microbial interactions
Canadian institutionsUniversity of Lethbridge
FundersMarsden FundNational Health and Medical Research CouncilBiomolecular Interaction Centre, University of CanterburyGöteborgs UniversitetState Government of VictoriaMassey UniversityMaurice Wilkins Centre for Molecular BiodiscoveryVINNOVACanterbury Medical Research FoundationAustralian SynchrotronMinistry of Business, Innovation and EmploymentCentre for Antibiotic Resistance Research, University of GothenburgUniversity of CanterburyNational Institutes of HealthNational Science Foundation
KeywordsSialic acidRepressorDNAAllosteric regulationBiologyPsychological repressionGeneBiochemistryEscherichia coliDNA-binding domainTranscription (linguistics)Operator (biology)Transcription factorEffectorCell biologyGene expressionEnzyme

Abstract

fetched live from OpenAlex

Abstract Bacteria respond to environmental changes by inducing transcription of some genes and repressing others. Sialic acids, which coat human cell surfaces, are a nutrient source for pathogenic and commensal bacteria. The Escherichia coli GntR-type transcriptional repressor, NanR, regulates sialic acid metabolism, but the mechanism is unclear. Here, we demonstrate that three NanR dimers bind a (GGTATA) 3 -repeat operator cooperatively and with high affinity. Truncation of an N-terminal extension abolishes cooperative binding. The effector, N -acetylneuraminate, binds NanR and attenuates DNA binding. Crystal structure data show that N -acetylneuraminate binding to NanR causes a domain rearrangement that locks the protein in a conformation that prevents DNA binding. Single-particle cryo-electron microscopy structures of NanR bound to DNA reveal the DNA binding domain is reorganized to engage DNA, while the three dimers assemble in close proximity across the (GGTATA) 3 -repeat operator allowing protein-protein interactions to form via the N-terminal extensions. Our data provides a molecular basis for the regulation of bacterial sialic acid metabolism.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

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)0.0020.001

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 head0.015
GPT teacher head0.212
Teacher spread0.197 · 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 source (direct Gemma or distilled Codex), 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

Citations2
Published2020
Admission routes1
Has abstractyes

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