The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages.
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...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0115344 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849332340039352320 |
|---|---|
| author | Mikael Altun Thomas S Walter Holger B Kramer Patrick Herr Alexander Iphöfer Johan Boström Yael David Alia Komsany Nicola Ternette Ami Navon David I Stuart Jingshan Ren Benedikt M Kessler |
| author_facet | Mikael Altun Thomas S Walter Holger B Kramer Patrick Herr Alexander Iphöfer Johan Boström Yael David Alia Komsany Nicola Ternette Ami Navon David I Stuart Jingshan Ren Benedikt M Kessler |
| author_sort | Mikael Altun |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-df235d64d4d94ee6b0d0d35d67ff82c0 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-df235d64d4d94ee6b0d0d35d67ff82c02025-08-20T03:46:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01101e011534410.1371/journal.pone.0115344The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages.Mikael AltunThomas S WalterHolger B KramerPatrick HerrAlexander IphöferJohan BoströmYael DavidAlia KomsanyNicola TernetteAmi NavonDavid I StuartJingshan RenBenedikt M KesslerOvarian 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.https://doi.org/10.1371/journal.pone.0115344 |
| spellingShingle | Mikael Altun Thomas S Walter Holger B Kramer Patrick Herr Alexander Iphöfer Johan Boström Yael David Alia Komsany Nicola Ternette Ami Navon David I Stuart Jingshan Ren Benedikt M Kessler The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages. PLoS ONE |
| title | The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages. |
| title_full | The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages. |
| title_fullStr | The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages. |
| title_full_unstemmed | The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages. |
| title_short | The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages. |
| title_sort | human otubain2 ubiquitin structure provides insights into the cleavage specificity of poly ubiquitin linkages |
| url | https://doi.org/10.1371/journal.pone.0115344 |
| work_keys_str_mv | AT mikaelaltun thehumanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT thomasswalter thehumanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT holgerbkramer thehumanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT patrickherr thehumanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT alexanderiphofer thehumanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT johanbostrom thehumanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT yaeldavid thehumanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT aliakomsany thehumanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT nicolaternette thehumanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT aminavon thehumanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT davidistuart thehumanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT jingshanren thehumanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT benediktmkessler thehumanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT mikaelaltun humanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT thomasswalter humanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT holgerbkramer humanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT patrickherr humanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT alexanderiphofer humanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT johanbostrom humanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT yaeldavid humanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT aliakomsany humanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT nicolaternette humanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT aminavon humanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT davidistuart humanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT jingshanren humanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages AT benediktmkessler humanotubain2ubiquitinstructureprovidesinsightsintothecleavagespecificityofpolyubiquitinlinkages |