E2 ubiquitin conjugating enzymes regulate the deubiquitinating activity of OTUB1
| Autor: | Michael J. Matunis, Reuven Wiener, Patrick M. Lombardi, Catherine M. Guzzo, Xiangbin Zhang, Cynthia Wolberger, Anthony T DiBello |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Protein Folding macromolecular substances Biology Ubiquitin-conjugating enzyme Crystallography X-Ray environment and public health Article Deubiquitinating enzyme Cell Line 03 medical and health sciences 0302 clinical medicine Ubiquitin Structural Biology Multienzyme Complexes Enzyme Stability Humans Protein Interaction Domains and Motifs Polyubiquitin Molecular Biology 030304 developmental biology chemistry.chemical_classification 0303 health sciences Deubiquitinating Enzymes Recombinant Proteins 3. Good health Ubiquitin ligase Ubiquitins Cysteine Endopeptidases Enzyme Biochemistry chemistry OTUB1 030220 oncology & carcinogenesis Ubiquitin-Conjugating Enzymes biology.protein Mutagenesis Site-Directed Protein folding HeLa Cells |
| Zdroj: | Nature structural & molecular biology |
| ISSN: | 1545-9985 1545-9993 |
| Popis: | OTUB1 is a Lys48-specific deubiquitinating enzyme that forms a complex in vivo with E2 ubiquitin (Ub)-conjugating enzymes including UBC13 and UBCH5. OTUB1 binds E2~Ub thioester intermediates and prevents ubiquitin transfer, thereby noncatalytically inhibiting accumulation of polyubiquitin. We report here that a second role of OTUB1-E2 interactions is to stimulate OTUB1 cleavage of Lys48 polyubiquitin. This stimulation is regulated by the ratio of charged to uncharged E2 and by the concentration of Lys48-linked polyubiquitin and free ubiquitin. Structural and biochemical studies of human and worm OTUB1 and UBCH5B show that the E2 enzyme stimulates binding of the Lys48 polyubiquitin substrate by stabilizing folding of the OTUB1 N-terminal ubiquitin-binding helix. Our results suggest that OTUB1-E2 complexes in the cell are poised to regulate polyubiquitin chain elongation or degradation in response to changing levels of E2 charging and available free ubiquitin. |
| Databáze: | OpenAIRE |
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