title: Structure of UBE2Z Enzyme Provides Functional Insight into Specificity in the FAT10 Protein Conjugation Machinery.
abstract: FAT10 conjugation, a post-translational modification analogous to ubiquitination, specifically requires UBA6 and UBE2Z as its activating (E1) and conjugating (E2) enzymes. Interestingly, these enzymes can also function in ubiquitination. We have determined the crystal structure of UBE2Z and report how the different domains of this E2 enzyme are organized. We further combine our structural data with mutational analyses to understand how specificity is achieved in the FAT10 conjugation pathway. We show that specificity toward UBA6 and UBE2Z lies within the C-terminal CYCI tetrapeptide in FAT10. We also demonstrate that this motif slows down transfer rates for FAT10 from UBA6 onto UBE2Z.
authors.affiliation: From the UMR8576 CNRS-Université de Lille, 50 Avenue de Halley, 59658 Villeneuve d'Ascq, France and.
authors.forename: Julien
authors.initials: J
authors.lastname: Schelpe
authors.affiliation: From the UMR8576 CNRS-Université de Lille, 50 Avenue de Halley, 59658 Villeneuve d'Ascq, France and.
authors.forename: Didier
authors.initials: D
authors.lastname: Monté
authors.affiliation: From the UMR8576 CNRS-Université de Lille, 50 Avenue de Halley, 59658 Villeneuve d'Ascq, France and.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Dewitte
authors.affiliation: Division of Biochemistry and Centre for Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Titia K
authors.initials: TK
authors.lastname: Sixma
authors.affiliation: From the UMR8576 CNRS-Université de Lille, 50 Avenue de Halley, 59658 Villeneuve d'Ascq, France and Division of Biochemistry and Centre for Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands prakash.rucktooa@univ-lille1.fr.
authors.forename: Prakash
authors.initials: P
authors.lastname: Rucktooa
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D007700:Kinetics; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry* / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; D010455:Peptides; D014452:Ubiquitins; D044763:Ubiquitin-Conjugating Enzymes; D044764:Ubiquitin-Activating Enzymes
keywords: FAT10; UBE2Z; UBL conjugation; crystal structure; post-translational modification (PTM); ubiquitin; ubiquitin-conjugating enzyme (E2 enzyme); ubiquitylation (ubiquitination)