Structural Insight into G-Protein Coupled Receptor Binding by Apelin
Bibliographic record
Abstract
Apelin peptides are the cognate ligands for the G-protein coupled receptor APJ, with functions in the cardiovascular and central nervous systems, in glucose metabolism and as a human immunodeficiency virus (HIV-1) coreceptor. Apelin is found in 13-36 residue forms in vivo. The structures of five isoforms of apelin at physiological versus low (5-6 degrees C) temperature are compared here using circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy, demonstrating increased structure at low temperature. Far-ultraviolet (UV) CD spectra are predominantly random coil for apelin isoforms, but are convoluted by unusual bands from the C-terminal phenylalanine side chain. These bands, assigned using F13A-apelin-13, are accentuated at 5 degrees C and imply conformational restriction. At 35 degrees C, the R6-L9 region of apelin-17 is well structured, consistent with previous mutagenesis results showing necessity of this segment for apelin-APJ binding and activation. At 5 degrees C, R6-L9 retains its structuring while the functionally critical C-terminal G13-F17 region also becomes highly structured. Type IV beta-turns and some polyproline-II structure alongside F17 side chain motional reduction correlate well with CD spectral properties. Cis-trans peptide bond isomerization at P14 and P16 produces two sequentially assignable conformers (both trans:both cis approximately 4:1) alongside less populated conformers. Chemical shift assignment of apelin-12, -13 and pyroglutamate-apelin-13 implies highly similar structuring and the same isomerization at the C-terminus. Based on the apelin-17 structure, a two-step binding and activation mechanism is hypothesized.
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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) | 0.001 | 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".