The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages.

2.50
Hdl Handle:
http://hdl.handle.net/10033/346874
Title:
The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages.
Authors:
Altun, Mikael; Walter, Thomas S; Kramer, Holger B; Herr, Patrick; Iphöfer, Alexander; Boström, Johan; David, Yael; Komsany, Alia; Ternette, Nicola; Navon, Ami; Stuart, David I; Ren, Jingshan; Kessler, Benedikt M
Abstract:
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages. 2015, 10 (1):e0115344 PLoS ONE
Journal:
PloS one
Issue Date:
2015
URI:
http://hdl.handle.net/10033/346874
DOI:
10.1371/journal.pone.0115344
PubMed ID:
25590432
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
Publications of Dept. Cell Biology (ZB)

Full metadata record

DC FieldValue Language
dc.contributor.authorAltun, Mikaelen
dc.contributor.authorWalter, Thomas Sen
dc.contributor.authorKramer, Holger Ben
dc.contributor.authorHerr, Patricken
dc.contributor.authorIphöfer, Alexanderen
dc.contributor.authorBoström, Johanen
dc.contributor.authorDavid, Yaelen
dc.contributor.authorKomsany, Aliaen
dc.contributor.authorTernette, Nicolaen
dc.contributor.authorNavon, Amien
dc.contributor.authorStuart, David Ien
dc.contributor.authorRen, Jingshanen
dc.contributor.authorKessler, Benedikt Men
dc.date.accessioned2015-03-19T14:36:15Zen
dc.date.available2015-03-19T14:36:15Zen
dc.date.issued2015en
dc.identifier.citationThe human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages. 2015, 10 (1):e0115344 PLoS ONEen
dc.identifier.issn1932-6203en
dc.identifier.pmid25590432en
dc.identifier.doi10.1371/journal.pone.0115344en
dc.identifier.urihttp://hdl.handle.net/10033/346874en
dc.description.abstractOvarian 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.en
dc.language.isoenen
dc.titleThe human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalPloS oneen

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