MétaCan
Menu
Back to cohort
Record W2099871879 · doi:10.3109/10409238.2011.636505

Proteins that bind and move lipids: MsbA and NPC1

2011· review· en· W2099871879 on OpenAlexaff
Gavin W. King, Frances J. Sharom

Bibliographic record

VenueCritical Reviews in Biochemistry and Molecular Biology · 2011
Typereview
Languageen
FieldMedicine
TopicLysosomal Storage Disorders Research
Canadian institutionsUniversity of Guelph
Fundersnot available
KeywordsNPC1FlippaseBiochemistryEndosomeMembrane proteinIntegral membrane proteinInner membraneBiologyBacterial outer membraneCell biologyPeripheral membrane proteinLipid bilayerTransport proteinPlant lipid transfer proteinsMembrane lipidsChemistryMembraneIntracellularPhospholipidEscherichia coli

Abstract

fetched live from OpenAlex

Membrane proteins that bind and transport lipids face special challenges. Since lipids typically have low water solubility, both accessibility of the substrate to the protein and delivery to the desired destination are problematical. The amphipathic nature of membrane lipids, and their relatively large molecular size, also means that these proteins must possess substrate-binding sites of a different nature than those designed to handle small polar molecules. This review considers two integral proteins whose function is to bind and transfer membrane lipids within or across a membrane. The first protein, MsbA, is a putative lipid flippase that is a member of the ATP-binding cassette (ABC) superfamily. The protein is found in the inner (cytoplasmic) membrane (IM) of Gram-negative bacteria such as E. coli, where it is proposed to move lipid A from the inner to the outer membrane (OM) leaflet, an important step in the lipopolysaccharide biosynthetic pathway. Cholesterol is a major component of the plasma membrane in eukaryotic cells, where it regulates bilayer fluidity. The other lipid-binding protein discussed here, mammalian NPC1 (Niemann-Pick disease, Type C1), binds cholesterol inside late endosomes/lysosomes (LE/LY) and is involved in its transfer to the cytosol as part of a key intracellular sterol-trafficking pathway. Mutations in NPC1 lead to a devastating neurodegenerative condition, Niemann-Pick Type C disease, which is characterized by massive cholesterol accumulation in LE/LY. The accelerating pace of membrane protein structure determination over the past decade has allowed us a glimpse of how lipid binding and transfer by membrane proteins such as MsbA and NPC1 might be achieved.

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)0.001
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.981
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
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 head0.073
GPT teacher head0.414
Teacher spread0.341 · 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 designNot applicable
Domainnot available
GenreReview

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

Citations27
Published2011
Admission routes1
Has abstractyes

Explore more

Same venueCritical Reviews in Biochemistry and Molecular BiologySame topicLysosomal Storage Disorders ResearchFrench-language works237,207