ArticleProceedings of the National Academy of Sciences of the United States of America2005
Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 186 citations in OpenAlex.
- Structural basis of signal peptide recognition by the signal peptidase complex.Nature communications · 2026Article
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- Article
- Rhomboid protease RHBDL4/RHBDD1 cleaves SREBP-1c at endoplasmic reticulum monitoring and regulating fatty acids.PNAS nexus · 2023Article
- The ERAD system is restricted by elevated ceramides.Science advances · 2023Article
- Chemical Blockage of the Mitochondrial Rhomboid Protease PARL by Novel Ketoamide Inhibitors Reveals Its Role in PINK1/Parkin-Dependent Mitophagy.Journal of medicinal chemistry · 2023Article
- Rhomboid-catalyzed intramembrane proteolysis requires hydrophobic matching with the surrounding lipid bilayer.Science advances · 2022Article
- Rhomboid protease RHBDL4 promotes retrotranslocation of aggregation-prone proteins for degradation.Cell reports · 2022Article
- Effect of Environmental Factors on the Catalytic Activity of Intramembrane Serine Protease.Journal of the American Chemical Society · 2022Article
- Phosphatidylglyerol Lipid Binding at the Active Site of an Intramembrane Protease.The Journal of membrane biology · 2020Review
- Rhomboid intramembrane protease YqgP licenses bacterial membrane protein quality control as adaptor of FtsH AAA protease.The EMBO journal · 2020Article
- The mitochondrial protein PGAM5 suppresses energy consumption in brown adipocytes by repressing expression of uncoupling protein 1.The Journal of biological chemistry · 2020Article
- Article
- Membrane cholesterol as regulator of human rhomboid protease RHBDL4.The Journal of biological chemistry · 2018Article
- Proteolytic ectodomain shedding of membrane proteins in mammals-hardware, concepts, and recent developments.The EMBO journal · 2018Review
- Embedded in the Membrane: How Lipids Confer Activity and Specificity to Intramembrane Proteases.The Journal of membrane biology · 2018Article
- Dynamic Water Hydrogen-Bond Networks at the Interface of a Lipid Membrane Containing Palmitoyl-Oleoyl Phosphatidylglycerol.The Journal of membrane biology · 2018Article
- Collagen-Induced Arthritis Analysis inBiomolecules & therapeutics · 2018Article
- Unwinding of the Substrate Transmembrane Helix in Intramembrane Proteolysis.Biophysical journal · 2018Article
- Discovery and Biological Evaluation of Potent and Selective N-Methylene Saccharin-Derived Inhibitors for Rhomboid Intramembrane Proteases.Biochemistry · 2017Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Intramembrane proteolysis is a new paradigm in biology that controls signaling events throughout evolution. Hydrolysis of peptide bonds is thought to occur within the normally hydrophobic membrane environment, but insights into this unusual activity have been lacking because of difficulty in recapitulating activity in vitro. We have reconstituted intramembrane proteolysis with a pure recombinant substrate and rhomboid proteins in both detergent micelles and artificial membrane environments. Rhomboid proteins from diverse organisms including two model bacteria, a pathogen, an extremophile, and an animal were robustly active in pure form, proving that rhomboids are a new class of enzymes and do not require cofactors to catalyze intramembrane proteolysis. Rhomboid proteins directly recognized their substrates in vitro by the top of the substrate transmembrane domain, displaying specificity apparently reciprocal to that of gamma-secretase, the only other activity known to cleave type-I transmembrane domains. Rhomboid proteases represent a different evolutionary path to a serine protease mechanism and exhibited an inhibitor profile unlike other serine proteases. Intriguingly, activity was dramatically modulated by different membrane phospholipid environments, suggesting a mechanism for regulating these proteases. This analysis promises to help reveal the biochemical mechanisms and biological roles of this most widely conserved membrane protein family.
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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.