An ankyrin-repeat ubiquitin-binding domain determines TRABID's specificity for atypical ubiquitin chains

Julien D F Licchesi, Juliusz Mieszczanek, Tycho E T Mevissen, Trevor J Rutherford, Masato Akutsu, Satpal Virdee, Farid El Oualid, Jason W Chin, Huib Ovaa, Mariann Bienz, David Komander

Research output: Contribution to journalArticlepeer-review

96 Citations (SciVal)


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.
Original languageEnglish
Pages (from-to)62-71
Number of pages10
JournalNature Structural and Molecular Biology
Issue number1
Early online date11 Dec 2011
Publication statusPublished - 2012


  • amino acid sequence
  • animals
  • ankyrin repeat
  • binding sites
  • blotting, western
  • COS cells
  • catalytic domain
  • cercopithecus aethiops
  • crystallography, X-ray
  • endopeptidases
  • fluorescence recovery after photobleaching
  • green fluorescent proteins
  • HEK293 cells
  • humans
  • lysine
  • magnetic resonance spectroscopy
  • microscopy, confocal
  • models, molecular
  • molecular sequence data
  • mutation
  • protein binding
  • protein structure, tertiary
  • sequence homology, amino acid
  • ubiquitin
  • ubiquitin thiolesterase


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