Methionine 170 is an Environmentally Sensitive Membrane Anchor in the Disordered HVR of K-Ras4B
Bibliographic record
Abstract
Ras protein colocalization at the plasma membrane is implicated in the activation of signaling cascades that promote cell growth, survival, and motility. However, the mechanisms that underpin Ras self-association remain unclear. We use molecular dynamics simulations to show how basic and hydrophobic components of the disordered C-terminal membrane tether of K-Ras4B combine to regulate its membrane interactions. Specifically, anionic lipids attract lysine residues to the membrane surface, thereby splitting the peptide population into two states that exchange on the microsecond time scale. These states differ in the membrane insertion of a methionine residue, which is influenced by local membrane composition. As a result, these states may impose context-dependent biases on the disposition of Ras' signaling domain, with possible implications for the accessibility of its effector binding surfaces. We investigate Ras' ability to nanocluster by fly-casting for patches of anionic lipids and find that while anionic lipids promote the intermolecular association of K-Ras4B membrane tethers, at short range this appears to be a passive process in which anionic lipids electrostatically screen these cationic peptides to mitigate their natural repulsion. Together with the sub-microsecond stability of interpeptide contacts, this result suggests that experimentally observed K-Ras4B nanoclustering is not driven by direct intermolecular contact of its membrane tethers.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".