ArticleNature2013
Mechanism of farnesylated CAAX protein processing by the intramembrane protease Rce1.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 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.
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Who cites it
87 citing papers in PubMed, 168 citations in OpenAlex.
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Structural insights into human signal peptide peptidase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Maize leaf yellowing gene ZmCAAX modulates growth and drought resistance by regulating abscisic acid contents through interaction with the ABA biosynthetic enzyme ZmNCED3.Plant biotechnology journal · 2025Article
- SpbR controls lipoteichoic acid length by directly inhibiting signal peptidase SpsB inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Maintaining the Integral Membrane Proteome: Revisiting the Functional Repertoire of Integral Membrane Proteases.Chembiochem : a European journal of chemical biology · 2025Review
- Myxosortase: an intramembrane protease that sorts MYXO-CTERM proteins to the cell surface.mBio · 2025Article
- Lawsonia intracellularis T3SS effector LI0758, an Rce1 ortholog, activates MAPK and NF-κB signaling in mammalian cells.Veterinary research · 2025Article
- Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets.Nature reviews. Cancer · 2024Review
- Article
- Unveiling a CAAX Protease-Like Protein Involved in Didemnin Drug Maturation and Secretion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The generation of detergent-insoluble clipped fragments from an ERAD substrate in mammalian cells.Scientific reports · 2023Article
- Decoding the crosstalk between mevalonate metabolism and T cell function.Immunological reviews · 2023Review
- The Advances and Limitations of the Determination and Applications of Water Structure in Molecular Engineering.International journal of molecular sciences · 2023Review
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- Live-Cell Sender-Receiver Co-cultures for Quantitative Measurement of Paracrine Signaling Dynamics, Gene Expression, and Drug Response.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The role of site-2-proteases in bacteria: a review on physiology, virulence, and therapeutic potential.microLife · 2023Review
- Conformational analysis and interaction of theFrontiers in chemistry · 2023Article
- RhoBTB3 Regulates Proliferation and Invasion of Breast Cancer Cells via Col1a1.Molecules and cells · 2022Article
- Article
- Conserved Proline Residues of Bacillus subtilis Intramembrane Metalloprotease SpoIVFB Are Important for Substrate Interaction and Cleavage.Journal of bacteriology · 2022Article
27 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
12 authors at 5 institutions in 2 countries.
Funding
Abstract
CAAX proteins have essential roles in multiple signalling pathways, controlling processes such as proliferation, differentiation and carcinogenesis. The ∼120 mammalian CAAX proteins function at cellular membranes and include the Ras superfamily of small GTPases, nuclear lamins, the γ-subunit of heterotrimeric GTPases, and several protein kinases and phosphatases. The proper localization of CAAX proteins to cell membranes is orchestrated by a series of post-translational modifications of the carboxy-terminal CAAX motifs (where C is cysteine, A is an aliphatic amino acid and X is any amino acid). These reactions involve prenylation of the cysteine residue, cleavage at the AAX tripeptide and methylation of the carboxyl-prenylated cysteine residue. The major CAAX protease activity is mediated by Rce1 (Ras and a-factor converting enzyme 1), an intramembrane protease (IMP) of the endoplasmic reticulum. Information on the architecture and proteolytic mechanism of Rce1 has been lacking. Here we report the crystal structure of a Methanococcus maripaludis homologue of Rce1, whose endopeptidase specificity for farnesylated peptides mimics that of eukaryotic Rce1. Its structure, comprising eight transmembrane α-helices, and catalytic site are distinct from those of other IMPs. The catalytic residues are located ∼10 Å into the membrane and are exposed to the cytoplasm and membrane through a conical cavity that accommodates the prenylated CAAX substrate. We propose that the farnesyl lipid binds to a site at the opening of two transmembrane α-helices, which results in the scissile bond being positioned adjacent to a glutamate-activated nucleophilic water molecule. This study suggests that Rce1 is the founding member of a novel IMP family, the glutamate IMPs.
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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.