Rhomboids are conserved intramembrane serine proteases with widespread functions. They were the earliest discovered members of the wider rhomboid-like superfamily of proteases and pseudoproteases. The secretase class of rhomboid proteases, distributed through the secretory pathway, are the most numerous in eukaryotes, but our knowledge of them is limited. Here we aim to summarise all that has been published on secretase rhomboids in a concise encyclopaedia of the enzymes, their substrates, and their biological roles. We also discuss emerging themes of how these important enzymes are regulated.
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http://dx.doi.org/10.1016/j.semcdb.2016.07.033 | DOI Listing |
Nucleic Acids Res
December 2024
Malaria Biochemistry Laboratory, The Francis Crick Institute, 1 Midland Road, NW1 1AT London, UK.
The malaria parasite needs nearly half of its genes to propagate normally within red blood cells. Inducible ways to interfere with gene expression like the DiCre-lox system are necessary to study the function of these essential genes. However, existing DiCre-lox strategies are not well-suited to be deployed at scale to study several genes simultaneously.
View Article and Find Full Text PDFACS Med Chem Lett
December 2024
Laboratory of Chemical Biology, Department of Cellular and Molecular Medicine, KU Leuven - University of Leuven, Herestraat 49 box 901b, 3000 Leuven, Belgium.
Rhomboid proteases play a variety of physiological roles, but rhomboid protease inhibitors have been mostly developed for the model rhomboid GlpG. In this work, we screened different electrophilic scaffolds against the human mitochondrial rhomboid PARL and found 4-oxo-β-lactams as submicromolar inhibitors. Multifaceted computations suggest explanations for the activity at the molecular scale and provide models of covalently bound complexes.
View Article and Find Full Text PDFSci Rep
November 2024
Department of Urology, The First Affiliated Hospital of Hainan Medical University, No. 31 Longhua Road, Longhua District, Haikou, 570102, Hainan Province, China.
The crosstalk between cuproptosis and the tumor immune microenvironment (TIME) is vital during clear cell renal cell carcinoma (ccRCC) malignant progression. However, the underlying molecular mechanisms regulate this cross-talk remain elusive. Through tailored machine learning, we analyze clinical ccRCC data from The Cancer Genome Atlas (TCGA) to explore the critical factors that regulate the interaction among cuproptosis, TIME, and tumor progression.
View Article and Find Full Text PDFBiophys J
December 2024
Institute for Medical Physics and Biophysics, University of Leipzig, Leipzig, Germany. Electronic address:
Cellular membranes exhibit a huge diversity of lipids and membrane proteins that differ in their properties and chemical structure. Cells organize these molecules into distinct membrane compartments characterized by specific lipid profiles and hydrophobic thicknesses of the respective domains. If a hydrophobic mismatch occurs between a membrane protein and the surrounding lipids, there can be functional consequences such as reduced protein activity.
View Article and Find Full Text PDFNat Commun
October 2024
Institute of Molecular Biochemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
The Golgi apparatus is essential for protein sorting, yet its quality control mechanisms are poorly understood. Here we show that the Dsc ubiquitin ligase complex uses its rhomboid pseudo-protease subunit, Dsc2, to assess the hydrophobic length of α-helical transmembrane domains (TMDs) at the Golgi. Thereby the Dsc complex likely interacts with orphaned ER and Golgi proteins that have shorter TMDs and ubiquitinates them for targeted degradation.
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