ArticleProceedings of the National Academy of Sciences of the United States of America2021
The KRAS and other prenylated polybasic domain membrane anchors recognize phosphatidylserine acyl chain structure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 42 citations in OpenAlex.
- Lipid nanoparticles as active biointerfaces: From membrane interaction to systemic dysregulation.Acta pharmaceutica Sinica. B · 2026Review
- KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment.Biomarker research · 2026Review
- Farnesol and geranylgeraniol in plant reproduction: insights from Arabidopsis and beyond.Journal of experimental botany · 2026Review
- KRAS G12C and KRAS G12D respond to lipid metabolism in an allele-specific manner.Journal of lipid research · 2026Article
- A cyclin-polarity feedback network ensures healthy cell proliferation.Nature communications · 2026Article
- Glycosphingolipids regulate phosphatidylserine transport machinery that operates at ER-PM contact sites.Nature communications · 2026Article
- Temperature and lipid composition differentially regulate KRAS assemblies on membranes.Chemical communications (Cambridge, England) · 2026Article
- KRAS4a and KRAS4b show distinct lipid-dependent regulation of RAS-RAF membrane dynamics.The Journal of biological chemistry · 2026Article
- ELOVL6 activity attenuation induces mutant KRAS degradation.Nature chemical biology · 2026Article
- Terraforming the KRAS lipid landscape.Nature chemical biology · 2026Article
- Dynamics and lipid membrane coupling of the RAS-RAF complex revealed via multiscale simulations.Biophysical journal · 2026Article
- Article
- RAS-membrane interaction and oligomerization: there is more than meets the eye.Biochemical Society transactions · 2025Review
- Drugging Ras trafficking-are there new roads to travel?npj drug discovery · 2025Review
- Kinesin-12 POK2 polarization is a prerequisite for a fully functional division site and aids cell plate positioning.Nature communications · 2025Article
- From disorder comes function: Regulation of small GTPase function by intrinsically disordered lipidated membrane anchor.Current opinion in structural biology · 2024Review
- Intrinsically Disordered Membrane Anchors of Rheb, RhoA, and DiRas3 Small GTPases: Molecular Dynamics, Membrane Organization, and Interactions.The journal of physical chemistry. B · 2024Article
- RAS G-domains allosterically contribute to the recognition of lipid headgroups and acyl chains.The Journal of cell biology · 2024Article
- Membrane-Driven Dimerization of the Peripheral Membrane Protein KRAS: Implications for Downstream Signaling.International journal of molecular sciences · 2024Review
- Native mass spectrometry of proteoliposomes containing integral and peripheral membrane proteins.Chemical science · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
KRAS interacts with the inner leaflet of the plasma membrane (PM) using a hybrid anchor that comprises a lysine-rich polybasic domain (PBD) and a C-terminal farnesyl chain. Electrostatic interactions have been envisaged as the primary determinant of interactions between KRAS and membranes. Here, we integrated molecular dynamics (MD) simulations and superresolution spatial analysis in mammalian cells and systematically compared four equally charged KRAS anchors: the wild-type farnesyl hexa-lysine and engineered mutants comprising farnesyl hexa-arginine, geranylgeranyl hexa-lysine, and geranylgeranyl hexa-arginine. MD simulations show that these equally charged KRAS mutant anchors exhibit distinct interactions and packing patterns with different phosphatidylserine (PtdSer) species, indicating that prenylated PBD-bilayer interactions extend beyond electrostatics. Similar observations were apparent in intact cells, where each anchor exhibited binding specificities for PtdSer species with distinct acyl chain compositions. Acyl chain composition determined responsiveness of the spatial organization of different PtdSer species to diverse PM perturbations, including transmembrane potential, cholesterol depletion, and PM curvature. In consequence, the spatial organization and PM binding of each KRAS anchor precisely reflected the behavior of its preferred PtdSer ligand to these same PM perturbations. Taken together these results show that small GTPase PBD-prenyl anchors, such as that of KRAS, have the capacity to encode binding specificity for specific acyl chains as well as lipid headgroups, which allow differential responses to biophysical perturbations that may have biological and signaling consequences for the anchored GTPase.
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