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Ubiquitylation

DUBs' key to selectivity

Nature Reviews Molecular Cell Biology volume 13, pages 64–65 (2012)Cite this article

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The authors first identified a stretch of ∼100 residues on the amino-terminal side of the TRABID OTU domain (the catalytic domain) that is absent from other OTU family DUBs (for example, A20). This extended catalytic domain cleaved Lys29- and Lys33-linked diubiquitin chains more efficiently than Lys63-linked chains or other linkages. Structural analysis revealed that this TRABID fragment contains two ankyrin repeats (motifs that promote protein–protein interactions), which, as the authors show for the first time, interact with ubiquitin.

So, is TRABID's specificity towards distinct atypical ubiquitin chains conferred by the domain containing the ankyrin repeats (AnkUBD)? The authors compared the in vitro enzymatic activity of full-length TRABID, of a fragment containing the AnkUBD and the OTU domain, and of the OTU domain alone. They observed that full-length TRABID and AnkUBD–OTU cleaved Lys29- and Lys33-linked diubiquitin (and Lys63-linked diubiquitin, but less efficiently) but not other ubiquitin chains, whereas the OTU domain alone could also hydrolyze other linkage types. Furthermore, TRABID's activity towards its diubiquitin substrates was reduced following removal of the AnkUBD or mutation of residues that interact with ubiquitin. These findings indicate that AnkUBD affects the catalytic activity of the OTU domain and restricts its linkage specificity, explaining TRABID's specificity towards a subset of atypical ubiquitin chains.

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References

ORIGINAL RESEARCH PAPER

  1. Licchesi, J. D. F. et al. An ankyrin-repeat ubiquitin-binding domain determines TRABID's specificity for atypical ubiquitin chains. Nature Struct. Mol. Biol. 11 Dec 2011 (doi:10.1038/nsmb.2169)

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FURTHER READING

  1. Komander, D., Clague, M. J. & Urbé, S. Breaking the chains: structure and function of the deubiquitinases. Nature Rev. Mol. Cell Biol. 10, 550–563 (2009)

    Article  CAS  Google Scholar 

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Authors
  1. Rachel David
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David, R. DUBs' key to selectivity. Nat Rev Mol Cell Biol 13, 64–65 (2012). https://doi.org/10.1038/nrm3268

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