The Proline-rich N-terminal Domain of G18 Exhibits a Novel G Protein Regulatory Function
Bibliographic record
Abstract
The protein G18 (also known as AGS4 or GPSM3) contains three conserved GoLoco/GPR domains in its central and C-terminal regions that bind to inactive Galpha(i), whereas the N-terminal region has not been previously characterized. We investigated whether this domain might itself regulate G protein activity by assessing the abilities of G18 and mutants thereof to modulate the nucleotide binding and hydrolytic properties of Galpha(i1) and Galpha(o). Surprisingly, in the presence of fluoroaluminate (AlF(4)(-)) both G proteins bound strongly to full-length G18 (G18wt) and to its isolated N-terminal domain (G18DeltaC) but not to its GoLoco region (DeltaNG18). Thus, it appears that its N-terminal domain promotes G18 binding to fluoroaluminate-activated Galpha(i/o). Neither G18wt nor any G18 mutant affected the GTPase activity of Galpha(i1) or Galpha(o). In contrast, complex effects were noted with respect to nucleotide binding. As inferred by the binding of [(35)S]GTPgammaS (guanosine 5'-O-[gamma-thio]triphosphate) to Galpha(i1), the isolated GoLoco region as expected acted as a guanine nucleotide dissociation inhibitor, whereas the N-terminal region exhibited a previously unknown guanine nucleotide exchange factor effect on this G protein. On the other hand, the N terminus inhibited [(35)S]GTPgammaS binding to Galpha(o), albeit to a lesser extent than the effect of the GoLoco region on Galpha(i1). Taken together, our results identify the N-terminal region of G18 as a novel G protein-interacting domain that may have distinct regulatory effects within the G(i/o) subfamily, and thus, it could potentially play a role in differentiating signals between these related G proteins.
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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 | 0.001 |
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".