2ZFY

Crystal structure of human Otubain 1

Summary for 2ZFY

• Entry DOI: 10.2210/pdb2zfy/pdb
• Descriptor: Ubiquitin thioesterase OTUB1 (2 entities in total)
• Functional Keywords: otu, otubain, structural genomics, structural genomics consortium, sgc, alternative splicing, hydrolase, immune response, phosphoprotein, protease, thiol protease, ubl conjugation pathway
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (By similarity): Q96FW1
• Total number of polymer chains: 1
• Total formula weight: 27129.46

Authors

Akutsu, M.,Walker, J.R.,Li, Y.,Weigelt, J.,Arrowsmith, C.H.,Edwards, A.M.,Bochkarev, A.,Dhe-Paganon, S.,Structural Genomics Consortium (SGC) (deposition date: 2008-01-16, release date: 2008-02-19, Last modification date: 2023-08-30)

Primary citation

Edelmann, M.J.,Iphofer, A.,Akutsu, M.,Altun, M.,di Gleria, K.,Kramer, H.B.,Fiebiger, E.,Dhe-Paganon, S.,Kessler, B.M.
Structural basis and specificity of human otubain 1-mediated deubiquitination.
Biochem.J., 418:379-390, 2009

PubMed Abstract: OTUB (otubain) 1 is a human deubiquitinating enzyme that is implicated in mediating lymphocyte antigen responsiveness, but whose molecular function is generally not well defined. A structural analysis of OTUB1 shows differences in accessibility to the active site and in surface properties of the substrate-binding regions when compared with its close homologue, OTUB2, suggesting variations in regulatory mechanisms and substrate specificity. Biochemical analysis reveals that OTUB1 has a preference for cleaving Lys(48)-linked polyubiquitin chains over Lys(63)-linked polyubiquitin chains, and it is capable of cleaving NEDD8 (neural-precursor-cell-expressed developmentally down-regulated 8), but not SUMO (small ubiquitin-related modifier) 1/2/3 and ISG15 (interferon-stimulated gene 15) conjugates. A functional comparison of OTUB1 and OTUB2 indicated a differential reactivity towards ubiquitin-based active-site probes carrying a vinyl methyl ester, a 2-chloroethyl or a 2-bromoethyl group at the C-terminus. Mutational analysis suggested that a narrow P1' site, as observed in OTUB1, correlates with its ability to preferentially cleave Lys(48)-linked ubiquitin chains. Analysis of cellular interaction partners of OTUB1 by co-immunoprecipitation and MS/MS (tandem mass spectrometry) experiments demonstrated that FUS [fusion involved in t(12;6) in malignant liposarcoma; also known as TLS (translocation in liposarcoma) or CHOP (CCAAT/enhancer-binding protein homologous protein)] and RACK1 [receptor for activated kinase 1; also known as GNB2L1 (guanine-nucleotide-binding protein beta polypeptide 2-like 1)] are part of OTUB1-containing complexes, pointing towards a molecular function of this deubiquitinating enzyme in RNA processing and cell adhesion/morphology.

PubMed: 18954305
DOI: 10.1042/BJ20081318

Experimental method

X-RAY DIFFRACTION (1.69 Å)