ArticleThe EMBO journal2014
Allosteric regulation of rhomboid intramembrane proteolysis.
Article in The EMBO journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 70 citations in OpenAlex.
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Transmembrane Parkinson's disease mutation of PINK1 leads to altered mitochondrial anchoring.The Journal of biological chemistry · 2025Article
- Evaluating the impact of the membrane thickness on the function of the intramembrane protease GlpG.Biophysical journal · 2024Article
- Lipid environment modulates processivity and kinetics of a presenilin homolog acting on multiple substrates in vitro.The Journal of biological chemistry · 2023Article
- Electrospray ionization of native membrane proteins proceedsRSC advances · 2022Article
- Effect of Environmental Factors on the Catalytic Activity of Intramembrane Serine Protease.Journal of the American Chemical Society · 2022Article
- The iRhom homology domain is indispensable for ADAM17-mediated TNFα and EGF receptor ligand release.Cellular and molecular life sciences : CMLS · 2021Article
- Membrane Protein Dimerization in Cell-Derived Lipid Membranes Measured by FRET with MC Simulations.Biophysical journal · 2020Article
- Involvement of a Membrane-Bound Amphiphilic Helix in Substrate Discrimination and Binding by anFrontiers in microbiology · 2020Article
- Substrate-Enzyme Interactions in Intramembrane Proteolysis: γ-Secretase as the Prototype.Frontiers in molecular neuroscience · 2020Review
- Modulating Hinge Flexibility in the APP Transmembrane Domain Alters γ-Secretase Cleavage.Biophysical journal · 2019Article
- Quantitative Multiplex Substrate Profiling of Peptidases by Mass Spectrometry.Molecular & cellular proteomics : MCP · 2019Article
- Understanding Conformational Dynamics of Complex Lipid Mixtures Relevant to Biology.The Journal of membrane biology · 2018Review
- Single-Molecule Analyses Reveal Rhomboid Proteins Are Strict and Functional Monomers in the Membrane.Biophysical journal · 2018Article
- Coupled Transmembrane Substrate Docking and Helical Unwinding in Intramembrane Proteolysis of Amyloid Precursor Protein.Scientific reports · 2018Article
- Unwinding of the Substrate Transmembrane Helix in Intramembrane Proteolysis.Biophysical journal · 2018Article
- Taking a position on intramembrane proteolysis.The Journal of biological chemistry · 2018Review
- Interaction of intramembrane metalloprotease SpoIVFB with substrate Pro-σProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Diacylglycerol Acyltransferase 1 Is Regulated by Its N-Terminal Domain in Response to Allosteric Effectors.Plant physiology · 2017Article
- Sensitive Versatile Fluorogenic Transmembrane Peptide Substrates for Rhomboid Intramembrane Proteases.The Journal of biological chemistry · 2017Article
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6 authors at 1 institution in 1 country.
Funding
Abstract
Proteolysis within the lipid bilayer is poorly understood, in particular the regulation of substrate cleavage. Rhomboids are a family of ubiquitous intramembrane serine proteases that harbour a buried active site and are known to cleave transmembrane substrates with broad specificity. In vitro gel and Förster resonance energy transfer (FRET)-based kinetic assays were developed to analyse cleavage of the transmembrane substrate psTatA (TatA from Providencia stuartii). We demonstrate significant differences in catalytic efficiency (kcat/K0.5) values for transmembrane substrate psTatA (TatA from Providencia stuartii) cleavage for three rhomboids: AarA from P. stuartii, ecGlpG from Escherichia coli and hiGlpG from Haemophilus influenzae demonstrating that rhomboids specifically recognize this substrate. Furthermore, binding of psTatA occurs with positive cooperativity. Competitive binding studies reveal an exosite-mediated mode of substrate binding, indicating allostery plays a role in substrate catalysis. We reveal that exosite formation is dependent on the oligomeric state of rhomboids, and when dimers are dissociated, allosteric substrate activation is not observed. We present a novel mechanism for specific substrate cleavage involving several dynamic processes including positive cooperativity and homotropic allostery for this interesting class of intramembrane proteases.
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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.