TM2-TM7 Interaction in Coupling Movement of Transmembrane Helices to Activation of the Angiotensin II Type-1 Receptor
Bibliographic record
Abstract
Agonist-induced rigid body motion of transmembrane (TM) helices has been established as a unifying mechanism in the activation of the G protein-coupled receptors. In attempts to measure specific conformational transitions during the activation of the type 1 receptor for angiotensin II (AT(1)), we found a decrease in accessibility of Cys(76) in the second TM helix, suggesting that the orientation of TM2 is altered (Miura, S., and Karnik, S. S. (2002) J. Biol. Chem. 277, 24299-24305). Now we provide evidence that the TM2 helical movement plays a role in regulating the activated state of the AT(1) receptor, and this role may involve an interaction between TM2 and TM7. Alanine substitution of native Cys(296) in TM7 leads to increased accessibility of Cys(289) and diminished response to bound agonist. Both effects of the C296A mutation are suppressed when combined with F77A and N111G mutants. The TM7 conformation and the sensitivity of Cys(289) altered by C296A mutation are suppressed by the F77A mutation in TM2 to salvage function. We show that the F77A mutant alters orientation of both TM2 and TM7 but does not induce constitutive activity in suppressing the C296A mutant effects. Thus, interaction of TM2 and TM7 is important for transmembrane signal transduction in the AT(1) receptor.
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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 | 0.001 | 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".