UBL/UBA ubiquitin receptor proteins bind a common tetraubiquitin chain

Yang Kang, Rebecca A. Vossler, Laura A. Diaz-Martinez, Nathan S. Winter, Duncan J. Clarke, Kylie J. Walters

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


The ubiquitin-proteasome pathway is essential throughout the life cycle of a cell. This system employs an astounding number of proteins to ubiquitylate and to deliver protein substrates to the proteasome for their degradation. At the heart of this process is the large and growing family of ubiquitin receptor proteins. Within this family is an intensely studied group that contains both ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains: Rad23, Ddi1 and Dsk2. Although UBL/UBA family members are reported to regulate the degradation of other proteins, their individual roles in ubiquitin-mediated protein degradation has proven difficult to resolve due to their overlapping functional roles and interaction with each other and other ubiquitin family members. Here, we use a combination of NMR spectroscopy and molecular biology to reveal that Rad23 and Ddi1 interact with each other by using UBL/UBA domain interactions in a manner that does not preclude their interaction with ubiquitin. We demonstrate that UBL/UBA proteins can bind a common tetraubiquitin molecule and thereby provide strong evidence for a model in which chains adopt an opened structure to bind multiple receptor proteins. Altogether our results suggest a mechanism through which UBL/UBA proteins could protect chains from premature de-ubiquitylation and unnecessary elongation during their transit to the proteasome.

Original languageEnglish (US)
Pages (from-to)1027-1035
Number of pages9
JournalJournal of Molecular Biology
Issue number4
StatePublished - Mar 3 2006

Bibliographical note

Funding Information:
We are grateful to Casey Litchke and Jeannette Zinggeler for assisting with the sample preparation. We also thank Dr Leonard Banaszak for allowing us to use his dynamic light-scattering instrument. NMR data were acquired at the NMR facility of the University of Minnesota and we thank Dr David Live and Dr Beverly Ostrowsky for their technical assistance. NMR instrumentation was provided with funds from the NSF (BIR-961477), the University of Minnesota Medical School, and the Minnesota Medical Foundation. Data processing and visualization were performed in the Basic Sciences Computing Laboratory of the University of Minnesota Supercomputing Institute. This work was funded by grants from the National Institutes of Health CA097004-01A1 (to K.J.W.) and CA099033 (to D.J.C.) as well as by a University of Minnesota Academic Health Center Seed Grant (to K.J.W.) and special grant from the University of Minnesota Cancer Center (to K.J.W. and D.J.C.).


  • Ddi1
  • Proteasome-mediated protein degradation
  • Rad23
  • Ubiquitin receptor proteins
  • Ubiquitin-associated domains


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