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

15 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Ubiquitin
Zinc Fingers
Proteins
Zinc
Biological Phenomena
Amino Acid Motifs
Post Translational Protein Processing
Degradation
Dimers
Chemical activation
Molecules

Keywords

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

ASJC Scopus subject areas

  • Biochemistry

Cite this

Searle, M. S., Garner, T. P., Strachan, J., Long, J., Adlington, J., Cavey, J. R., ... 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

Structural insights into specificity and diversity in mechanisms of ubiquitin recognition by ubiquitin-binding domains. / Searle, Mark S.; Garner, Thomas P.; Strachan, Joanna; Long, Jed; Adlington, Jennifer; Cavey, James R.; Shaw, Barry; Layfield, Robert.

In: Biochemical Society Transactions, Vol. 40, No. 2, 04.2012, p. 404-408.

Research output: Contribution to journalReview article

Searle, MS, Garner, TP, Strachan, J, Long, J, Adlington, J, Cavey, JR, Shaw, B & Layfield, R 2012, 'Structural insights into specificity and diversity in mechanisms of ubiquitin recognition by ubiquitin-binding domains', Biochemical Society Transactions, vol. 40, no. 2, pp. 404-408. https://doi.org/10.1042/BST20110729
Searle, Mark S. ; Garner, Thomas P. ; Strachan, Joanna ; Long, Jed ; Adlington, Jennifer ; Cavey, James R. ; Shaw, Barry ; Layfield, Robert. / Structural insights into specificity and diversity in mechanisms of ubiquitin recognition by ubiquitin-binding domains. In: Biochemical Society Transactions. 2012 ; Vol. 40, No. 2. pp. 404-408.
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