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  • The EMBO Journal (2003) 22, 4634 - 4645
  • doi:10.1093/emboj/cdg467

Structural determinants for the binding of ubiquitin-like domains to the proteasome

Thomas D. Mueller2 and Juli Feigon1

  1. Department of Chemistry and Biochemistry, 405 Hilgard Avenue, PO Box 951569, University of California, Los Angeles, CA 90095-1569, USA
  2. Present address: Department of Physiological Chemistry II, Biocenter, Am Hubland, D-97074 Wuerzburg, Germany

Correspondence to:

Juli Feigon, E-mail: feigon@mbi.ucla.edu

Received 3 June 2003; Accepted 28 July 2003; Revised 23 July 2003

HHR23A, a protein implicated in nucleotide excision repair, belongs to a class of proteins containing both a ubiquitin-like (Ubl) domain and one or more ubiquitin-associated (UBA) domains, suggesting a role in the ubiquitin–proteasome pathway as well. The Ubl domain binds with high affinity to the second ubiquitin-interacting motif (UIM) of the S5a subunit of the proteasome. Here we present the solution structures of the HHR23A Ubl domain, the second UIM of S5a (UIM-2), and the Ubl:S5a–UIM-2 complex. The HHR23A Ubl domain is structurally similar to ubiquitin. The S5a UIM forms an alpha-helix with an unexpected hairpin loop that contributes to the binding interface with Ubl. The molecular determinants of the Ubl–proteasome interaction are revealed by analysis of the structures, chemical shift mapping, mutant binding studies and sequence conservation.

  • Keywords:

    • NMR,
    • protein degradation,
    • Rad23,
    • S5a,
    • Ubl