Structure of UBE2Z Enzyme Provides Functional Insight into Specificity in the FAT10 Protein Conjugation Machinery |
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Authors: | Julien Schelpe Didier Monté Frédérique Dewitte Titia K Sixma Prakash Rucktooa |
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Institution: | 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 |
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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. |
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Keywords: | crystal structure post-translational modification (PTM) ubiquitin ubiquitin-conjugating enzyme (E2 enzyme) ubiquitylation (ubiquitination) FAT10 UBE2Z UBL conjugation |
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