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

Mikael Altun, Thomas S. Walter, Holger B. Kramer, Patrick Herr, Alexander Iphoefer, Johan Bostrom, Yael David, Alia Komsany, Nicola Ternette, Ami Navon, David I. Stuart, Jingshan Ren, Benedikt M. Kessler

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere0115344
JournalPLoS ONE
Volume10
Issue number1
DOIs
StatePublished - 14 Jan 2015

All Science Journal Classification (ASJC) codes

  • General

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