ArticleThe EMBO journal2008
A novel switch region regulates H-ras membrane orientation and signal output.
Article in The EMBO journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
121 citing papers in PubMed, 203 citations in OpenAlex.
- KRAS G12C and KRAS G12D respond to lipid metabolism in an allele-specific manner.Journal of lipid research · 2026Article
- Mechanistic insights on spatiotemporal control of Ras-signaling.Biological chemistry · 2026Review
- Rheb membrane orientation dynamics and functional consequences elucidated by molecular simulations, single-molecule-FRET and signaling assays.bioRxiv : the preprint server for biology · 2026Article
- Development of a Genetically Encoded and Potent PDE6D Inhibitor.Chembiochem : a European journal of chemical biology · 2025Article
- Identification and characterization of binders to a cryptic and functional pocket in KRAS.Nature communications · 2025Article
- The impact of RAS on cell differentiation in health and disease.The Biochemical journal · 2025Review
- RAS-membrane interaction and oligomerization: there is more than meets the eye.Biochemical Society transactions · 2025Review
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- SHANK3 depletion leads to ERK signalling overdose and cell death in KRAS-mutant cancers.Nature communications · 2024Article
- RAS G-domains allosterically contribute to the recognition of lipid headgroups and acyl chains.The Journal of cell biology · 2024Article
- GTP-Bound N-Ras Conformational States and Substates Are Modulated by Membrane and Point Mutation.International journal of molecular sciences · 2024Article
- Structural and functional analyses of a germline KRAS T50I mutation provide insights into Raf activation.JCI insight · 2023Article
- RAS GTPases and Interleaflet Coupling in the Plasma Membrane.Cold Spring Harbor perspectives in biology · 2023Review
- Direct Observation of Membrane-Associated H-Ras in the Native Cellular Environment by In-CellJACS Au · 2023Article
- RAS nanoclusters are cell surface transducers that convert extracellular stimuli to intracellular signalling.FEBS letters · 2023Review
- Eliminating oncogenic RAS: back to the future at the drawing board.Biochemical Society transactions · 2023Article
- Exploring CRD mobility during RAS/RAF engagement at the membrane.Biophysical journal · 2022Article
- Structural insights into Ras regulation by SIN1.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The plasma membrane nanoscale distribution of H-ras is regulated by guanine nucleotide binding. To explore the structural basis of H-ras membrane organization, we combined molecular dynamic simulations and medium-throughput FRET measurements on live cells. We extracted a set of FRET values, termed a FRET vector, to describe the lateral segregation and orientation of H-ras with respect to a large set of nanodomain markers. We show that mutation of basic residues in helix alpha4 or the hypervariable region (HVR) selectively alter the FRET vectors of GTP- or GDP-loaded H-ras, demonstrating a critical role for these residues in stabilizing GTP- or GDP-H-ras interactions with the plasma membrane. By a similar analysis, we find that the beta2-beta3 loop and helix alpha5 are involved in a novel conformational switch that operates through helix alpha4 and the HVR to reorient the H-ras G-domain with respect to the plasma membrane. Perturbation of these switch elements enhances MAPK activation by stabilizing GTP-H-ras in a more productive signalling conformation. The results illustrate how the plasma membrane spatially constrains signalling conformations by acting as a semi-neutral interaction partner.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.