4FJV

Crystal Structure of Human Otubain2 and Ubiquitin Complex

Summary for 4FJV

• Entry DOI: 10.2210/pdb4fjv/pdb
• Descriptor: Ubiquitin thioesterase OTUB2, Polyubiquitin-C, GLYCEROL, ... (5 entities in total)
• Functional Keywords: ubiquitin, otubain, nedd8, cleavage specificity, deubiquitylation, cysteine protease, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Ubiquitin: Cytoplasm : P0CG48
• Total number of polymer chains: 4
• Total formula weight: 75307.37

Authors

Altun, M.,Walter, T.S.,Kramer, H.B.,Iphofer, A.,David, Y.,Komsany, A.,Ternette, N.,Nicholson, B.,Navon, A.,Stuart, D.I.,Ren, J.,Kessler, B.M. (deposition date: 2012-06-12, release date: 2013-06-12, Last modification date: 2023-09-13)

Primary citation

Altun, M.,Walter, T.S.,Kramer, H.B.,Herr, P.,Iphofer, A.,Bostrom, J.,David, Y.,Komsany, A.,Ternette, N.,Navon, A.,Stuart, D.I.,Ren, J.,Kessler, B.M.
The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages.
Plos One, 10:e0115344-e0115344, 2015

PubMed 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.

PubMed: 25590432
DOI: 10.1371/journal.pone.0115344

Experimental method

X-RAY DIFFRACTION (2.047 Å)