TY - JOUR
T1 - An ankyrin-repeat ubiquitin-binding domain determines TRABID's specificity for atypical ubiquitin chains
AU - Licchesi, Julien D.F.
AU - Mieszczanek, Juliusz
AU - Mevissen, Tycho E.T.
AU - Rutherford, Trevor J.
AU - Akutsu, Masato
AU - Virdee, Satpal
AU - Oualid, Farid El
AU - Chin, Jason W.
AU - Ovaa, Huib
AU - Bienz, Mariann
AU - Komander, David
PY - 2012/1
Y1 - 2012/1
N2 - Eight different types of ubiquitin linkages are present in eukaryotic cells that regulate diverse biological processes. Proteins that mediate specific assembly and disassembly of atypical Lys6, Lys27, Lys29 and Lys33 linkages are mainly unknown. We here reveal how the human ovarian tumor (OTU) domain deubiquitinase (DUB) TRABID specifically hydrolyzes both Lys29-and Lys33-linked diubiquitin. A crystal structure of the extended catalytic domain reveals an unpredicted ankyrin repeat domain that precedes an A20-like catalytic core. NMR analysis identifies the ankyrin domain as a new ubiquitin-binding fold, which we have termed AnkUBD, and DUB assays in vitro and in vivo show that this domain is crucial for TRABID efficiency and linkage specificity. Our data are consistent with AnkUBD functioning as an enzymatic S1' ubiquitin-binding site, which orients a ubiquitin chain so that Lys29 and Lys33 linkages are cleaved preferentially.
AB - Eight different types of ubiquitin linkages are present in eukaryotic cells that regulate diverse biological processes. Proteins that mediate specific assembly and disassembly of atypical Lys6, Lys27, Lys29 and Lys33 linkages are mainly unknown. We here reveal how the human ovarian tumor (OTU) domain deubiquitinase (DUB) TRABID specifically hydrolyzes both Lys29-and Lys33-linked diubiquitin. A crystal structure of the extended catalytic domain reveals an unpredicted ankyrin repeat domain that precedes an A20-like catalytic core. NMR analysis identifies the ankyrin domain as a new ubiquitin-binding fold, which we have termed AnkUBD, and DUB assays in vitro and in vivo show that this domain is crucial for TRABID efficiency and linkage specificity. Our data are consistent with AnkUBD functioning as an enzymatic S1' ubiquitin-binding site, which orients a ubiquitin chain so that Lys29 and Lys33 linkages are cleaved preferentially.
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U2 - 10.1038/nsmb.2169
DO - 10.1038/nsmb.2169
M3 - Article
C2 - 22157957
AN - SCOPUS:84855465067
SN - 1545-9993
VL - 19
SP - 62
EP - 72
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 1
ER -