ArticleNature2018
Atomic structure of the eukaryotic intramembrane RAS methyltransferase ICMT.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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
26 citing papers in PubMed, 42 citations in OpenAlex.
- The Underexplored Mechanobiology of Lamin A Biogenesis and Homeostasis.Biology of the cell · 2026Review
- ICMT supports BRAFProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting ICMT: A promising strategy in cancer treatment (Review).Oncology letters · 2026Review
- Update of the Methyltransferase Gene Family: Classification, Evolution and Biological Functions.Human genomics · 2026Review
- Electron transfer engineering of artificially designed cell factory for complete biosynthesis of steroids.Nature communications · 2025Article
- Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets.Nature reviews. Cancer · 2024Review
- Surface-active antibiotic production as a multifunctional adaptation for postfire microorganisms.The ISME journal · 2024Article
- Yeast as a tool for membrane protein production and structure determination.FEMS yeast research · 2022Article
- Methyltransferases: Functions and Applications.Chembiochem : a European journal of chemical biology · 2022Review
- Licoricidin combats gastric cancer by targeting the ICMT/Ras pathway in vitro and in vivo.Frontiers in pharmacology · 2022Article
- Monobodies as tool biologics for accelerating target validation and druggable site discovery.RSC medicinal chemistry · 2021Review
- Post-translational modification of KRAS: potential targets for cancer therapy.Acta pharmacologica Sinica · 2021Review
- Post-translational Modifications of the Protein Termini.Frontiers in cell and developmental biology · 2021Review
- Structure of human steroid 5α-reductase 2 with the anti-androgen drug finasteride.Nature communications · 2020Article
- A Novel KRAS Antibody Highlights a Regulation Mechanism of Post-Translational Modifications of KRAS during Tumorigenesis.International journal of molecular sciences · 2020Article
- Structure and Mechanism of DHHC Protein Acyltransferases.Journal of molecular biology · 2020Review
- Article
- Improved Protocol for the Production of the Low-Expression Eukaryotic Membrane Protein Human Aquaporin 2 inBiomolecules · 2020Article
- KRAS G12C Game of Thrones, which direct KRAS inhibitor will claim the iron throne?Cancer treatment reviews · 2020Review
- DHHC20 Palmitoyl-Transferase Reshapes the Membrane to Foster Catalysis.Biophysical journal · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The maturation of RAS GTPases and approximately 200 other cellular CAAX proteins involves three enzymatic steps: addition of a farnesyl or geranylgeranyl prenyl lipid to the cysteine (C) in the C-terminal CAAX motif, proteolytic cleavage of the AAX residues and methylation of the exposed prenylcysteine residue at its terminal carboxylate. This final step is catalysed by isoprenylcysteine carboxyl methyltransferase (ICMT), a eukaryote-specific integral membrane enzyme that resides in the endoplasmic reticulum. ICMT is the only cellular enzyme that is known to methylate prenylcysteine substrates; methylation is important for the biological functions of these substrates, such as the membrane localization and subsequent activity of RAS, prelamin A and RAB. Inhibition of ICMT has potential for combating progeria and cancer. Here we present an X-ray structure of ICMT, in complex with its cofactor, an ordered lipid molecule and a monobody inhibitor, at 2.3 Å resolution. The active site spans cytosolic and membrane-exposed regions, indicating distinct entry routes for the cytosolic methyl donor, S-adenosyl-l-methionine, and for prenylcysteine substrates, which are associated with the endoplasmic reticulum membrane. The structure suggests how ICMT overcomes the topographical challenge and unfavourable energetics of bringing two reactants that have different cellular localizations together in a membrane environment-a relatively uncharacterized but defining feature of many integral membrane enzymes.
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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.