title: Structural insights into specificity and diversity in mechanisms of ubiquitin recognition by ubiquitin-binding domains.
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 Asp58/Gln62. 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 Ile44/Val70 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.
authors.affiliation: Centre for Biomolecular Sciences, School of Chemistry, University of Nottingham, Nottingham NG7 2RD, U.K. mark.searle@nottingham.ac.uk
authors.forename: Mark S
authors.initials: MS
authors.lastname: Searle
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Garner
authors.forename: Joanna
authors.initials: J
authors.lastname: Strachan
authors.forename: Jed
authors.initials: J
authors.lastname: Long
authors.forename: Jennifer
authors.initials: J
authors.lastname: Adlington
authors.forename: James R
authors.initials: JR
authors.lastname: Cavey
authors.forename: Barry
authors.initials: B
authors.lastname: Shaw
authors.forename: Robert
authors.initials: R
authors.lastname: Layfield
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009154:Mutation / Q000235:genetics; D010001:Osteitis Deformans / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D025801:Ubiquitin