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Protein degradation

Catching ubiquitin

Nature Reviews Molecular Cell Biology volume 9, pages 498–499 (2008)Cite this article

Rpn13 is a high-affinity receptor for ubiquitin...

Using a yeast two-hybrid assay, Husnjak et al. found that a conserved N-terminal region of human RPN13 interacts with ubiquitin. To test whether Rpn13 binds ubiquitin chains in the context of intact proteasomes, the authors first purified proteasomes from a yeast rpn13Δ mutant and assayed ubiquitin-chain binding. They observed a reduction in ubiquitin-binding by rpn13Δ proteasomes, which is comparable to that observed in mutants of Rpn10, the only other proteasomal component known to function as ubiquitin receptor. Addition of recombinant Rpn13 to the rpn13Δ proteasome rescued the binding defect, thereby confirming that Rpn13 is a ubiquitin receptor. Analysis of the protein structure of yeast Rpn13 revealed that the N terminus of Rpn13, which binds to ubiquitin, has a configuration similar to the pleckstrin-homology domain (PHD). Therefore the authors named this domain pleckstrin-like receptor for ubiquitin (Pru). This is the first example of a PHD structure being found within the proteasome. In a separate study, Schreiner et al. found that murine Pru adopts a PHD fold structure and binds Lys48-linked diubiquitin with high affinity. In contrast to all other ubiquitin-binding proteins, RPN13 does not use α-helices to bind to ubiquitin, but instead uses the loop regions of the Pru. Mutants with amino-acid substitutions in the Pru loops did not bind to ubiquitin, which confirms that the loop regions of Pru are responsible for this interaction. Husnjak et al. determined the ubiquitin-binding residues of yeast Pru and showed that their mutation impairs binding.

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References

ORIGINAL RESEARCH PAPERS

  1. Husnjak, K. et al. Proteasome subunit Rpn13 is a novel ubiquitin receptor. Nature 453, 481–488 (2008)

    Article  CAS  Google Scholar 

  2. Schreiner, P. et al. Ubiquitin docking at the proteasome through a novel pleckstrin-homology domain interaction. Nature 453, 548–552 (2008)

    Article  CAS  Google Scholar 

FURTHER READING

  1. Hicke, L., Schubert, H. L. & Hill, C. P. Ubiquitin-binding domains. Nature Rev. Mol. Cell Biol. 6, 610–621 (2005)

    Article  CAS  Google Scholar 

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Authors
  1. Francesca Cesari
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Cesari, F. Catching ubiquitin. Nat Rev Mol Cell Biol 9, 498–499 (2008). https://doi.org/10.1038/nrm2431

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