000008254 001__ 8254
000008254 005__ 20240329141309.0
000008254 0247_ $$2DOI$$a10.6083/pk02cb30t
000008254 037__ $$aIR
000008254 041__ $$aeng
000008254 245__ $$aDeciphering atypical ubiquitin signals using pathogen-derived E3 ligases
000008254 260__ $$bOregon Health and Science University
000008254 269__ $$a2020
000008254 336__ $$aAbstract
000008254 520__ $$aUbiquitin is a small 8 kDa protein that is appended onto lysine residues of proteins as a post-translational modification, and functions in regulating diverse cellular processes. Through its own lysine residues or its N-terminus, ubiquitin can be joined into one of eight distinct polymeric chains using multiple ubiquitin monomers. Extensive research has led to an understanding of the cellular functions for some of the eight chains, but the biology of the remaining chains remain mysterious. Ubiquitin chains are generated by the incredibly diverse E3 ubiquitin ligating enzymes, each of which contain some level of specificity for a particular ubiquitin chain. One obstacle impairing the study for some of the mysterious chains is the lack of a known eukaryotic E3 ligase that generates the chain preferentially. Fortuitously, many pathogenic bacteria have convergently evolved E3 ligases to co-opt the ubiquitin system of eukaryotic hosts to aid in establishing infection, enabling an alternative approach to study ubiquitin chain ligation. Here, we use protein mutagenesis techniques on E3 ligases from enterohemorrhagic Escherichia coli, Salmonella Typhimurium, and other pathogenic bacteria to explore the structural determinants of the mysterious Lys6-linked ubiquitin chains. Further, we report and utilize a novel E3 ligase with strong preference for Lys6-linked chain ligation, greater than that of any E3 ligase to our knowledge. Dysregulation of the ubiquitin cycle is implicated in numerous cancers, neurodegenerative diseases and autoimmune disorders, and by exploring the elusive Lys6-linked ubiquitin chain, our work expands the toolbox for decoding the ubiquitin system and its contributions to human health.
000008254 540__ $$fCC BY
000008254 542__ $$fIn copyright - joint owners
000008254 650__ $$aBacteria$$015323
000008254 650__ $$aFluorescence$$019121
000008254 650__ $$aUbiquitins$$027542
000008254 6531_ $$ae3 ligase
000008254 6531_ $$aprotein
000008254 691__ $$aSchool of Medicine$$041369
000008254 692__ $$aDepartment of Molecular Microbiology and Immunology$$041429
000008254 7001_ $$aFranklin, Tyler$$uOregon Health and Science University$$041354
000008254 7001_ $$aPruneda, Jonathan$$uOregon Health and Science University$$041354
000008254 711__ $$aResearch Week$$uOregon Health and Science University$$d2020
000008254 8564_ $$9ef5c72c1-c0f9-49f6-bd3d-dde2139b4889$$s45616$$uhttps://digitalcollections.ohsu.edu/record/8254/files/Tyler-Franklin.pdf
000008254 905__ $$a/rest/prod/pk/02/cb/30/pk02cb30t
000008254 980__ $$aResearch Week