Conformation and ion transport of neuronal uncoupling proteins: UCP2, UCP4, and UCP5
Bibliographic record
Abstract
Located in the inner mitochondrial membrane of brown adipose tissue, uncoupling protein -1 (UCP1) dissipates the proton electrochemical gradient, causing reduction in the rate of ATP synthesis, and generates heat by non-shivering thermogenesis. Three other UCP homologs (UCP2, UCP4 and UCP5), expressed in neurons, are suggested to have potential roles in the function and protection of the central nervous system (CNS). Up to date, structural information for UCPs still remains limited. Extensive biochemical studies on UCP2 have provided adequate evidence for its participation in proton and anion transport. So far, no functional studies in proteoliposome systems have been performed on UCP4 and UCP5. Thus, the goals of this study are to gain further information on the conformations and functional properties of neuronal UCPs reconstituted in liposomes. The emphasis is on UCP4 and UCP5 and their comparison to UCP2. Recombinant versions of all neuronal UCPs were successfully expressed, purified and reconstituted in azolectin liposomes (with and without the supplement of 2.5 mol% cardiolipin). UCP2 and UCP4 showed a high α-helical content in liposomes, while UCP5 conformation was less helical, with conformations exhibiting β-sheet characteristics. Ion transport assays (proton and chloride) for reconstituted neuronal UCPs were successfully developed using anion-sensitive fluorescent probes. All neuronal UCPs displayed proton transport across the membrane with characteristics similar to the archetypical protein UCP1, which is activated by fatty acids and inhibited by purine nucleotides. Chloride anion transport is also shown for UCP2 and UCP4. In addition, it was observed that the mitochondrial lipid cardiolipin (CL) induced drastic changes in conformation and ion transport of reconstituted UCPs. A hypothesized interaction mechanism of UCPs and CL was drawn from experimental results and molecular modelling. Overall, this study has provided a detailed picture of the conformation and ion transport properties of neuronal UCPs in liposomes, and also emphasizes the crucial role of cardiolipin in UCP structure and function.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".