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Diverse polyubiquitin interaction properties of ubiquitin-associated domains

Nature Structural & Molecular Biology volume 12, pages 708–714 (2005)Cite this article

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 (∼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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Figure 1: Diverse polyubiquitin interaction preferences of mammalian UBA domains.
Figure 2: Conservation of UBA domain interaction properties in budding yeast.
Figure 3: Robust binding of monoubiquitin and polyubiquitin chains to UQ1-UBA.
Figure 4: NMR analysis of UBA-monoubiquitin interactions.
Figure 5: Interaction properties of UBA-containing proteins.

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Acknowledgements

We thank K. Hofmann for communicating the alignment shown in Supplementary Figure 1 and for helpful discussions. We are grateful to the many colleagues who provided reagents for these studies, and to R. Cohen for comments on the manuscript. This work was supported by US National Institutes of Health (NIH) grants to C.M.P. (GM60372 and U54 RR020839) and D.F. (GM65334). The Biacore 3000 was purchased with funds from the NIH (S10 RR019046).

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  1. Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, 21205, Maryland, USA

    Shahri Raasi & Cecile M Pickart

  2. Department of Chemistry and Biochemistry, Center of Biomolecular Structure and Organization, University of Maryland, College Park, 20742, Maryland, USA

    Ranjani Varadan & David Fushman

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Correspondence to Cecile M Pickart.

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Supplementary information

Supplementary Fig. 1

UBA domains surveyed for polyubiquitin chain-binding properties. (PDF 54 kb)

Supplementary Fig. 2

Mono-ubiquitin binding to selected UBA domains. (PDF 35 kb)

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Raasi, S., Varadan, R., Fushman, D. et al. Diverse polyubiquitin interaction properties of ubiquitin-associated domains. Nat Struct Mol Biol 12, 708–714 (2005). https://doi.org/10.1038/nsmb962

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