ArticleProceedings of the National Academy of Sciences of the United States of America2012
Organization, dynamics, and segregation of Ras nanoclusters in membrane domains.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 177 citations in OpenAlex.
- Condensates and cell states: A new paradigm for understanding tumor biology.Biophysical journal · 2026Review
- Farnesol and geranylgeraniol in plant reproduction: insights from Arabidopsis and beyond.Journal of experimental botany · 2026Review
- Mechanistic insights on spatiotemporal control of Ras-signaling.Biological chemistry · 2026Review
- Apical and basolateral plasma membranes in epithelial cells have distinct lipidomes and biophysical properties.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Pharmacological tools to modulate ordered membrane domains and order-dependent protein function.Communications chemistry · 2026Article
- Apical and basolateral plasma membranes in epithelial cells have distinct lipidomes and biophysical properties.bioRxiv : the preprint server for biology · 2025Article
- PROTEIN-PROTEIN INTERACTION NETWORKS CAN BE HIGHLY SENSITIVE TO THE MEMBRANE PHASE TRANSITION.bioRxiv : the preprint server for biology · 2025Article
- Protein-protein interaction networks can be highly sensitive to the membrane phase transition.ArXiv · 2025Article
- Pharmacological Tools to Modulate Ordered Membrane Domains and Order-Dependent Protein Function.bioRxiv : the preprint server for biology · 2025Article
- RAS-membrane interaction and oligomerization: there is more than meets the eye.Biochemical Society transactions · 2025Review
- Greasing the wheels of inflammasome formation: regulation of NLRP3 function by S-linked fatty acids.Biochemical Society transactions · 2025Article
- Small-Molecule Modulators of Lipid Raft Stability and Protein-Raft Partitioning.bioRxiv : the preprint server for biology · 2024Article
- Exploring the Role of Hydroxy- and Phosphate-TerminatedACS polymers Au · 2024Article
- RAS G-domains allosterically contribute to the recognition of lipid headgroups and acyl chains.The Journal of cell biology · 2024Article
- Dysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk.The FEBS journal · 2024Review
- Effect of Impurities on the Formation of End-Group Clusters in Natural Rubber: Phenylalanine Dipeptide as an Impurity Protein.Macromolecules · 2024Article
- GTP-Bound N-Ras Conformational States and Substates Are Modulated by Membrane and Point Mutation.International journal of molecular sciences · 2024Article
- Understanding the free-energy landscape of phase separation in lipid bilayers using molecular dynamics.Biophysical journal · 2023Article
- Conformational ensemble-dependent lipid recognition and segregation by prenylated intrinsically disordered regions in small GTPases.Communications biology · 2023Article
- RAS GTPases and Interleaflet Coupling in the Plasma Membrane.Cold Spring Harbor perspectives in biology · 2023Review
46 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Recent experiments have shown that membrane-bound Ras proteins form transient, nanoscale signaling platforms that play a crucial role in high-fidelity signal transmission. However, a detailed characterization of these dynamic proteolipid substructures by high-resolution experimental techniques remains elusive. Here we use extensive semiatomic simulations to reveal the molecular basis for the formation and domain-specific distribution of Ras nanoclusters. As model systems, we chose the triply lipidated membrane targeting motif of H-ras (tH) and a large bilayer made up of di160-PC (DPPC), di182-PC (DLiPC), and cholesterol. We found that 4-10 tH molecules assemble into clusters that undergo molecular exchange in the sub-μs to μs time scale, depending on the simulation temperature and hence the stability of lipid domains. Driven by the opposite preference of tH palmitoyls and farnesyl for ordered and disordered membrane domains, clustered tH molecules segregate to the boundary of lipid domains. Additionally, a systematic analysis of depalmitoylated and defarnesylated tH variants allowed us to decipher the role of individual lipid modifications in domain-specific nanocluster localization and thereby explain why homologous Ras isoforms form nonoverlapping nanoclusters. Moreover, the localization of tH nanoclusters at domain boundaries resulted in a significantly lower line tension and increased membrane curvature. Taken together, these results provide a unique mechanistic insight into how protein assembly promoted by lipid-modification modulates bilayer shape to generate functional signaling platforms.
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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.