Structural insights into specificity and diversity in mechanisms of ubiquitin recognition by ubiquitin-binding domains

Mark S. Searle, Thomas P. Garner, Joanna Strachan, Jed Long, Jennifer Adlington, James R. Cavey, Barry Shaw, Robert Layfield

Research output: Contribution to journalReview article

16 Scopus citations

Abstract

UBDs [Ub (ubiquitin)-binding domains], which are typically small protein motifs of <50 residues, are used by receptor proteins to transduce post-translational Ub modifications in a wide range of biological processes, including NF-κB (nuclear factor κB) signalling and proteasomal degradation pathways. More than 20 families of UBDs have now been characterized in structural detail and, although many recognize the canonical Ile44/Val70-binding patch on Ub, a smaller number have alternative Ub-recognition sites. The A20 Znf (A20-like zinc finger) of the ZNF216 protein is one of the latter and binds with high affinity to a polar site on Ub centred around Asp 58/Gln 62. ZNF216 shares some biological function with p62, with both linked to NF-κB signal activation and as shuttle proteins in proteasomal degradation pathways. The UBA domain (Ub-associated domain) of p62, although binding to Ub through the Ile 44/Val 70 patch, is unique in forming a stable dimer that negatively regulates Ub recognition. We show that the A20 Znf and UBA domain are able to form a ternary complex through independent interactions with a single Ub molecule, supporting functional models for Ub as a 'hub' for mediating multi-protein complex assembly and for enhancing signalling specificity.

Original languageEnglish (US)
Pages (from-to)404-408
Number of pages5
JournalBiochemical Society transactions
Volume40
Issue number2
DOIs
StatePublished - Apr 2012

Keywords

  • Atrogene
  • NMR spectroscopy
  • Paget's disease of bone (PDB)
  • Sequestosome 1 (SQSTM1)
  • Ubiquitin-associated domain (UBA domain)
  • p62

ASJC Scopus subject areas

  • Biochemistry

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    Searle, M. S., Garner, T. P., Strachan, J., Long, J., Adlington, J., Cavey, J. R., Shaw, B., & Layfield, R. (2012). Structural insights into specificity and diversity in mechanisms of ubiquitin recognition by ubiquitin-binding domains. Biochemical Society transactions, 40(2), 404-408. https://doi.org/10.1042/BST20110729