| Structural highlights
Function
OTUB2_HUMAN Hydrolase that can remove conjugated ubiquitin from proteins in vitro and may therefore play an important regulatory role at the level of protein turnover by preventing degradation. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains, with a preference for 'Lys-63'-linked polyubiquitin chains.[1] [2]
Publication Abstract from PubMed
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.
The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages.,Altun M, Walter TS, Kramer HB, Herr P, Iphofer A, Bostrom J, David Y, Komsany A, Ternette N, Navon A, Stuart DI, Ren J, Kessler BM PLoS One. 2015 Jan 15;10(1):e0115344. doi: 10.1371/journal.pone.0115344., eCollection 2015. PMID:25590432[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Balakirev MY, Tcherniuk SO, Jaquinod M, Chroboczek J. Otubains: a new family of cysteine proteases in the ubiquitin pathway. EMBO Rep. 2003 May;4(5):517-22. PMID:12704427 doi:10.1038/sj.embor.embor824
- ↑ Edelmann MJ, Iphofer A, Akutsu M, Altun M, di Gleria K, Kramer HB, Fiebiger E, Dhe-Paganon S, Kessler BM. Structural basis and specificity of human otubain 1-mediated deubiquitination. Biochem J. 2009 Mar 1;418(2):379-90. PMID:18954305 doi:10.1042/BJ20081318
- ↑ Altun M, Walter TS, Kramer HB, Herr P, Iphofer A, Bostrom J, David Y, Komsany A, Ternette N, Navon A, Stuart DI, Ren J, Kessler BM. The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages. PLoS One. 2015 Jan 15;10(1):e0115344. doi: 10.1371/journal.pone.0115344., eCollection 2015. PMID:25590432 doi:http://dx.doi.org/10.1371/journal.pone.0115344
|
