Article

Diverse polyubiquitin interaction properties of ubiquitin-associated domains

Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, Maryland 21205, USA.
Nature Structural & Molecular Biology (Impact Factor: 11.63). 09/2005; 12(8):708-14. DOI: 10.1038/nsmb962
Source: PubMed

ABSTRACT The ubiquitin-associated (UBA) domain occurs frequently in proteins involved in ubiquitin-dependent signaling pathways. Although polyubiquitin chain binding is considered to be a defining feature of the UBA domain family, the generality of this property has not been established. Here we have surveyed the polyubiquitin interaction properties of 30 UBA domains, including 16 of 17 occurrences in budding yeast. The UBA domains sort into four classes that include linkage-selective polyubiquitin binders and domains that bind different chains (and monoubiquitin) in a nondiscriminatory manner; one notable class ( approximately 30%) did not bind any ubiquitin ligand surveyed. The properties of a given UBA domain are conserved from yeast to mammals. Their functional relevance is further suggested by the ability of an ectopic UBA domain to alter the specificity of a deubiquitylating enzyme in a predictable manner. Conversely, non-UBA sequences can modulate the interaction properties of a UBA domain.

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    • "To increase the binding affinity between F box proteins and their ubiquitinated substrates, we fused a ubiquitin-associated (UBA) domain from the soluble ubiquitin receptor Dsk2 or Rad23 to F box proteins (Figure 1A). These UBAs have a strong preference for polyubiquitin but bind both the K48-and K63- linked forms (Raasi et al., 2005; Sims et al., 2009). Using three tandem Flag epitopes as a linker, we fused the amino terminus of the F box protein Cdc4 to the tandem UBAs of Rad23 (Rad23-Fl-Cdc4). "
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    • "The UBA2 domain of hHR23a binds preferentially to K48-linked chains (Raasi et al., 2005) and in a sandwich-like mode involving contacts with the hydrophobic patches of both Ub units and the linker region (Varadan et al., 2005). UBA2 also binds specifically but weakly to both monoUb (Mueller et al., 2004; Ryu et al., 2003) and K63-Ub 2 (Varadan et al., 2004). "
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    • "The UBDs UBA (ubiquitin-associated) (Madura, 2002) and CUE (Ponting, 2000; Shih et al., 2003) interact with ubiquitin via a similar three a helix bundle, whereas other UBDs bind ubiquitin via a different tertiary structure (Randles and Walters, 2012; Searle et al., 2012). The affinity for both mono-or polyubiquitylated substrates and differently linked ubiquitin chains can vary greatly (Raasi et al., 2005; Dikic and Dö tsch, 2009; Husnjak and Dikic, 2012). "
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