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Record W3208434813 · doi:10.1101/2021.10.22.465361

FABP7 Binds to Fatty Acid Micelles: Implications for Lipid Transport

2021· preprint· en· W3208434813 on OpenAlexaff
Stefan A. P. Lenz, Iulia Bodnariuc, Margaret Renaud‐Young, Tanille M. Shandro, Justin L. MacCallum

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPeroxisome Proliferator-Activated Receptors
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsMicroscale thermophoresisFatty acid-binding proteinFatty acidBiochemistryMicelleDocosahexaenoic acidChemistryNile redCytoplasmTransporterBiophysicsTransport proteinPolyunsaturated fatty acidBiologyFluorescenceOrganic chemistry

Abstract

fetched live from OpenAlex

Abstract The transport of hydrophobic molecules, including long-chain fatty acids, within cells is highly dynamic. Hydrophobic molecules are unable to freely diffuse through the aqueous cytoplasm without a transporter. Fatty acid binding proteins (FABP) transport these molecules to different cellular compartments. As part of their transport, FABPs often associate with cell membranes to acquire and deliver their bound cargo. Understanding the nature of this transport is becoming increasingly important because lipid signaling functions are associated with metabolic pathways impacting disease pathologies such as carcinomas, autism and schizophrenia. Herein, we focus on Brain fatty acid binding protein (FABP7), which demonstrates localization to the cytoplasm and nucleus, influencing transcription and fatty acid metabolism. We use a combined biophysical approach to elucidate the interaction between FABP7 and model membranes. Specifically, we use microscale thermophoresis to show that FABP7 can bind oleic acid (OA) and docosahexaenoic acid (DHA) micelles, while differential scanning fluorimetry experiments show binding lowers the melting temperature of FABP7. Structural data from NMR and multiscale molecular dynamics simulations reveals that the interaction between FABP7 and micelles is through FABP7’s portal region residues. Our simulations also capture binding events where fatty acids dissociate from the model membrane and bind to FABP7. Overall, our data reveals a novel interaction between FABP7 and OA or DHA micelles and provides key structural insight into the transport of hydrophobic molecules. Significance This study examines how FABP7 binds to fatty acids at low and high fatty acid concentrations. Our binding assays, including microscale thermophoresis (MST) and Nile red fluorescence establish that FABP7 binds to both free fatty acids in solution and fatty acid micelles. NMR and computational experiments show that FABP7 specifically interacts with micelles through the portal region of the protein, thereby mediating ligand transfer into the binding cavity.

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 score0.004
Threshold uncertainty score0.007

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 studies0.0010.000
Scholarly communication0.0000.001
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.014
GPT teacher head0.240
Teacher spread0.226 · 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
Published2021
Admission routes1
Has abstractyes

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