The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages
| Autor: | Nicola Ternette, Jingshan Ren, Ami Navon, Alia Komsany, Alexander Iphöfer, Yael David, Patrick Herr, Mikael Altun, Thomas S. Walter, Benedikt M. Kessler, Johan Boström, David I. Stuart, Holger B. Kramer |
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| Přispěvatelé: | Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular Multidisciplinary biology Ubiquitin binding Ubiquitin Science Ubiquitin-conjugating enzyme Crystallography X-Ray ISG15 Enzyme structure Protein Structure Tertiary Ubiquitin ligase Deubiquitinating enzyme Biochemistry OTUB1 biology.protein Humans Medicine Thiolester Hydrolases Polyubiquitin Research Article Protein Binding |
| Zdroj: | PLoS ONE, Vol 10, Iss 1, p e0115344 (2015) PLoS ONE |
| Popis: | Ovarian tumor domain containing proteases cleave ubiquitin (Ub) and ubiquitin-like polypeptides from proteins. Here we report the crystal structure of human otubain 2 (OTUB2) in complex with a ubiquitin-based covalent inhibitor, Ub-Br2. The ubiquitin binding mode is oriented differently to how viral otubains (vOTUs) bind ubiquitin/ISG15, and more similar to yeast and mammalian OTUs. In contrast to OTUB1 which has exclusive specificity towards Lys48 poly-ubiquitin chains, OTUB2 cleaves different poly-Ub linked chains. N-terminal tail swapping experiments between OTUB1 and OTUB2 revealed how the N-terminal structural motifs in OTUB1 contribute to modulating enzyme activity and Ub-chain selectivity, a trait not observed in OTUB2, supporting the notion that OTUB2 may affect a different spectrum of substrates in Ub-dependent pathways. |
| Databáze: | OpenAIRE |
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