Bicelle composition-dependent modulation of phospholipid dynamics by apelin peptides
Bibliographic record
Abstract
Apelin peptides are cognate ligands for the apelin receptor, a G-protein-coupled receptor (GPCR). The apelinergic system plays critical roles in wide-ranging physiological activities including function and development of the central nervous and cardiovascular systems. Apelin is found in 13–55 residue isoforms in vivo, all of which share the C-terminal portion of the preproapelin precursor. Characterization of high-resolution structures and detergent micelle interactions of apelin-17 led to a two-step membrane-catalyzed binding and GPCR activation mechanism hypothesis recapitulated in longer isoforms. Here, we examine interactions of the apelin-13 and -17 isoforms with isotropic zwitterionic and mixed zwitterionic–anionic lipid bicelles to test for hallmarks of membrane catalysis in a more physiological membrane-mimetic environment than a micelle. Specifically, 1 H and 31 P relaxation and diffusion solution-state NMR techniques demonstrate that both apelin isoforms interact with both types of isotropic bicelles. Bicelle hydrodynamics were observed to be differentially modulated by apelin peptides, although these effects were minimal. Phospholipid headgroup 31 P spin relaxation behaviour was, conversely, clearly perturbed. Perturbation of this nature was also observed in magnetically aligned bicelles by 31 P solid-state NMR spectroscopy and spin relaxation experiments. This behaviour is consistent with an apelin–bicelle binding process allowing significant peptide mobility, facilitating membrane-catalyzed GPCR encounter.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| 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 | 0.001 |
| 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 teacher head, 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".