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Record W2119417279 · doi:10.1002/prot.22606

Holo‐BtuF stabilizes the open conformation of the vitamin B12 ABC transporter BtuCD

2009· article· en· W2119417279 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueProteins Structure Function and Bioinformatics · 2009
Typearticle
Languageen
FieldMedicine
TopicDrug Transport and Resistance Mechanisms
Canadian institutionsUniversity of Calgary
FundersCanadian Institutes of Health ResearchAlberta Heritage Foundation for Medical Research
KeywordsTransporterTransmembrane domainMolecular dynamicsChemistryStereochemistryDocking (animal)Transmembrane proteinCrystallographyATP-binding cassette transporterTransport proteinConformational changeProtein structureProtein subunitBiophysicsBiochemistryMembraneBiologyComputational chemistryGene

Abstract

fetched live from OpenAlex

While there is evidence that other ABC transporters can tell between empty and loaded substrate binding protein, reconstitution experiments suggest otherwise for the Escherichia coli vitamin B12 importer BtuCD-F. Here, we address the question of BtuCD-F substrate sensitivity in a combined protein-protein docking and molecular dynamics simulation approach. Starting from the BtuCD and holo-BtuF crystal structures, we model two holo-BtuCD-F docking complexes differing by a 180 degrees orientation of BtuF. One of these is similar to the apo-BtuCD-F crystal structure. Both docking complexes were embedded in a lipid/water environment to investigate their dynamics and BtuCD's conformational response to the presence and absence of BtuF, vitamin B12, and Mg-ATP in a series of 28 independent MD simulations. We find holo-BtuF stabilizing the open conformation of BtuCD, whereas the transporter begins to close again when BtuF or vitamin B12 is removed-suggesting BtuCD-F is capable of substrate sensitivity. We identified BtuC transmembrane helices 3 and 5, the L-loops and the adjacent helices comprised of BtuC residues 170-180 as hotspots of conformational change. We propose the latter to act as substrate sensors. BtuF-Trp44 appears to act as a lid on the vitamin B12 binding cleft in BtuF X-ray structures and protrudes into the BtuCD transport channel in one of our simulations, which might represent an initial step in vitamin B12 uptake. On an average, we observe subunit motions where the nucleotide binding domains approach each other while the transmembrane domains display an opening trend toward the periplasm.

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.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.754
Threshold uncertainty score0.304

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 science0.0000.000
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 head0.009
GPT teacher head0.222
Teacher spread0.213 · 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