Parasitic arthropods feed on blood or skin tissue and share comparable repertoires of proteases involved in haematophagy, digestion, egg development and immunity. While proteolytically active proteases of multiple classes dominate, an increasing number of pseudoproteases have been discovered that have no proteolytic function but are pharmacologically active biomolecules, evolved to carry out alternative functions as regulatory, antihaemostatic, anti-inflammatory or immunomodulatory compounds. In this review, we provide an overview of proteases and pseudoproteases from clinically important arthropod parasites. Many of these act in central biological pathways of parasite survival and host-parasite interaction and may be potential targets for therapeutic interventions.
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http://dx.doi.org/10.1111/febs.15546 | DOI Listing |
Nat 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.
View Article and Find Full Text PDFPhysiol Plant
May 2024
Department of Chemistry, Umeå University, Umeå, Sweden.
With climate change, droughts are expected to be more frequent and severe, severely impacting plant biomass and quality. Here, we show that overexpressing the Arabidopsis gene AtFtsHi3 (FtsHi3OE) enhances drought-tolerant phenotypes without compromising plant growth. AtFtsHi3 encodes a chloroplast envelope pseudo-protease; knock-down mutants (ftshi3-1) are found to be drought tolerant but exhibit stunted growth.
View Article and Find Full Text PDFMol Cell
June 2024
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Electronic address:
A disintegrin and metalloprotease 17 (ADAM17) is a membrane-tethered protease that triggers multiple signaling pathways. It releases active forms of the primary inflammatory cytokine tumor necrosis factor (TNF) and cancer-implicated epidermal growth factor (EGF) family growth factors. iRhom2, a rhomboid-like, membrane-embedded pseudoprotease, is an essential cofactor of ADAM17.
View Article and Find Full Text PDFMol Cell
January 2024
Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Electronic address:
iRhoms are pseudoprotease members of the rhomboid-like superfamily and are cardinal regulators of inflammatory and growth factor signaling; they function primarily by recognizing transmembrane domains of their clients. Here, we report a mechanistically distinct nuclear function of iRhoms, showing that both human and mouse iRhom2 are non-canonical substrates of signal peptidase complex (SPC), the protease that removes signal peptides from secreted proteins. Cleavage of iRhom2 generates an N-terminal fragment that enters the nucleus and modifies the transcriptome, in part by binding C-terminal binding proteins (CtBPs).
View Article and Find Full Text PDFAdv Biol Regul
May 2024
University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur (C.G), 492010, India. Electronic address:
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