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The Human Otubain2-Ubiquitin Structure Provides Insights into the Cleavage Specificity of Poly-Ubiquitin-Linkages

DOI: 10.1371/journal.pone.0115344 DOI Help
PMID: 25590432 PMID Help

Authors: Mikael Altun (University of Oxford) , Thomas Walter (University of Oxford) , Holger B. Kramer (University of Oxford) , P Herr (Karolinska Institutet, Sweden) , Alexander Iphöfer (Helmholtz Centre for Infection Research) , Johan Boström (Karolinska Institutet, Sweden) , Yael David (The Weizmann Institute of Science, Israel) , Alia Komsany (University of Oxford) , Nicola Ternette (University of Oxford) , Ami Navon (The Weizmann Institute of Science, Israel) , Dave Stuart (Diamond Light Source) , Jingshan Ren (University of Oxford) , Benedikt M. Kessler (University of Oxford) , Jamil Saad
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Plos One , VOL 10

State: Published (Approved)
Published: January 2015
Diamond Proposal Number(s): 10627

Open Access Open Access

Abstract: Ovarian tumor domain containing proteases cleave ubiquitin (Ub) and ubiquitin-like poly- peptides 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 ori- ented 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.

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)