5txk | pdb_00005txk

CRYSTAL STRUCTURE OF USP35 C450S IN COMPLEX WITH UBIQUITIN

spinqualitylabelsall models 5txk, resolution 1.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5txk is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.84Å Ligands: EDO, SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function UBP35_HUMAN Publication Abstract from PubMed Protein ubiquitylation is a dynamic post-translational modification that can be reversed by deubiquitylating enzymes (DUBs). It is unclear how the small number of approximately 100 DUBs present in mammalian cells regulates the thousands of different ubiquitylation events. Here we analysed annotated transcripts of human DUBs and find approximately 300 ribosome-associated transcripts annotated as protein coding, which thus increase the total number of DUBs. Using USP35, a poorly studied DUB, as a case study we provide evidence that alternative isoforms contribute to the functional expansion of DUBs. We show the existence of two different USP35 isoforms that localise to different intracellular compartments and have distinct functions. Our results reveal that isoform 1 is an anti-apoptotic factor that inhibits staurosporine- and TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis. In contrast, USP35 isoform 2 is an integral membrane protein of the endoplasmic reticulum (ER) present also at lipid droplets. Manipulations of isoform 2 levels cause rapid ER stress likely through deregulation of lipid homeostasis and lead to cell death. Our work highlights how alternative isoforms provide functional expansion of DUBs and sets directions for future research. Expansion of DUB functionality by alternative isoforms: USP35, a case study.,Leznicki P, Natarajan J, Bader G, Spevak W, Schlattl A, Rehman SAA, Pathak D, Weidlich S, Zoephel A, Bordone MC, Barbosa-Morais NL, Boehmelt G, Kulathu Y J Cell Sci. 2018 Apr 23. pii: jcs.212753. doi: 10.1242/jcs.212753. PMID:29685892 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thioesterase 3D structures

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