Role of the Palmitoyl Group and of the Amphipathic α Helix in the Membrane Binding of the C-Terminus of G-Protein Receptor Kinase 4α/β
Bibliographic record
Abstract
Membrane binding of monotopic proteins can involve various post-translational modifications or a combination of some membrane-binding elements. For example, amphipathic α helices and palmitoylation could drive the membrane attachment of proteins. G-protein-coupled receptor kinases (GRKs) regulate the activity of G-protein-coupled receptors. Several members of the family of GRKs are acylated. Moreover, the C-terminus of GRK6 contains an amphipathic α helix and a palmitoyl group, which could also be the case for GRK4 isoforms. In our experiments, GRK4α/β-derived peptides of differing C-terminal lengths (Cter-GRK4α/β variants) were thus studied to discriminate the individual role of the palmitoyl group and amphipathic α helix of Cter-GRK4α/β in its membrane binding. The membrane binding of the Cter-GRK4α/β variants was studied by comparing their maximum insertion pressure (MIP) to lipid monolayers as well as their intrinsic fluorescence properties using large unilamellar vesicles. The MIP data show a higher level of binding of the palmitoylated longest GRK4α/β variant. Moreover, MIP measurements in the absence and presence of 15 mol % of the negatively charged phosphoserine demonstrated that the amphipathic α helix of Cter-GRK4α/β plays a major role in its membrane binding. Accordingly, partition studies of the Cter-GRK4α/β variants to membranes by fluorescence spectroscopy demonstrate the involvement of the palmitoyl group and the amphipathic α helix of the C-terminus of GRK4α/β in its membrane binding. Altogether, the data show that both the palmitoyl group and the amphipathic helix highly favor membrane binding of the C-terminus of GRK4α/β, which should facilitate the proper anchoring of GRK4α/β and phosphorylation of GPCRs.
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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 | 0.001 |
| 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".