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The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages.
Altun, Mikael Walter, Thomas S Kramer, Holger B Herr, Patrick Iphöfer, Alexander Boström, Johan David, Yael Komsany, Alia Ternette, Nicola Navon, Ami
Altun, Mikael
Walter, Thomas S
Kramer, Holger B
Herr, Patrick
Iphöfer, Alexander
Boström, Johan
David, Yael
Komsany, Alia
Ternette, Nicola
Navon, Ami
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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.
Citation
The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages. 2015, 10 (1):e0115344 PLoS ONE
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en
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1932-6203