ArticleeLife2012
Membrane immersion allows rhomboid proteases to achieve specificity by reading transmembrane segment dynamics.
Article in eLife, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 100 citations in OpenAlex.
- Charting γ-secretase substrates by explainable AI.Nature communications · 2025Article
- Rhomboid-mediated cleavage of the immune receptor XA21 protects grain set and male fertility in rice.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Dsc complex and its role in Golgi quality control.Biochemical Society transactions · 2024Review
- The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi.Nature communications · 2024Article
- Lipid-polymer nanoparticles to probe the native-like environment of intramembrane rhomboid protease GlpG and its activity.Nature communications · 2024Article
- Cryo-EM reveals that iRhom2 restrains ADAM17 protease activity to control the release of growth factor and inflammatory signals.Molecular cell · 2024Article
- Rhomboid protease RHBDL4/RHBDD1 cleaves SREBP-1c at endoplasmic reticulum monitoring and regulating fatty acids.PNAS nexus · 2023Article
- The opening dynamics of the lateral gate regulates the activity of rhomboid proteases.Science advances · 2023Article
- Conformational surveillance of Orai1 by a rhomboid intramembrane protease prevents inappropriate CRAC channel activation.Molecular cell · 2021Article
- Proteins associated with the Arabidopsis thaliana plastid rhomboid-like protein RBL10.The Plant journal : for cell and molecular biology · 2021Article
- Derlin rhomboid pseudoproteases employ substrate engagement and lipid distortion to enable the retrotranslocation of ERAD membrane substrates.Cell reports · 2021Article
- Decoding the Functional Evolution of an Intramembrane Protease Superfamily by Statistical Coupling Analysis.Structure (London, England : 1993) · 2020Article
- Designed Parasite-Selective Rhomboid Inhibitors Block Invasion and Clear Blood-Stage Malaria.Cell chemical biology · 2020Article
- The role of rhomboid superfamily members in protein homeostasis: Mechanistic insight and physiological implications.Biochimica et biophysica acta. Molecular cell research · 2020Review
- Bacterial rhomboid proteases mediate quality control of orphan membrane proteins.The EMBO journal · 2020Article
- Article
- Multiple downy mildew effectors target the stress-related NAC transcription factor LsNAC069 in lettuce.The Plant journal : for cell and molecular biology · 2019Article
- A predicted plastid rhomboid protease affects phosphatidic acid metabolism in Arabidopsis thaliana.The Plant journal : for cell and molecular biology · 2019Article
- Modulating Hinge Flexibility in the APP Transmembrane Domain Alters γ-Secretase Cleavage.Biophysical journal · 2019Article
- The rhomboid protease GlpG has weak interaction energies in its active site hydrogen bond network.The Journal of general physiology · 2019Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Rhomboid proteases reside within cellular membranes, but the advantage of this unusual environment is unclear. We discovered membrane immersion allows substrates to be identified in a fundamentally-different way, based initially upon exposing 'masked' conformational dynamics of transmembrane segments rather than sequence-specific binding. EPR and CD spectroscopy revealed that the membrane restrains rhomboid gate and substrate conformation to limit proteolysis. True substrates evolved intrinsically-unstable transmembrane helices that both become unstructured when not supported by the membrane, and facilitate partitioning into the hydrophilic, active-site environment. Accordingly, manipulating substrate and gate dynamics in living cells shifted cleavage sites in a manner incompatible with extended sequence binding, but correlated with a membrane-and-helix-exit propensity scale. Moreover, cleavage of diverse non-substrates was provoked by single-residue changes that destabilize transmembrane helices. Membrane immersion thus bestows rhomboid proteases with the ability to identify substrates primarily based on reading their intrinsic transmembrane dynamics.DOI:http://dx.doi.org/10.7554/eLife.00173.001.
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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.