DUBs' key to selectivity | Nature Reviews Molecular Cell Biology

Access through your institution Buy or subscribe 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. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print

issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to

local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES ORIGINAL

RESEARCH PAPER * 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) Article  Google Scholar  FURTHER READING * 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  Download references Authors * Rachel David View author publications You can also search for this author inPubMed 

Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE David, R. DUBs' key to selectivity. _Nat Rev Mol Cell Biol_ 13, 64–65 (2012).

https://doi.org/10.1038/nrm3268 Download citation * Published: 30 December 2011 * Issue Date: February 2012 * DOI: https://doi.org/10.1038/nrm3268 SHARE THIS ARTICLE Anyone you share the

following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer

Nature SharedIt content-sharing initiative