The structure of the 26S proteasome subunit Rpn2 reveals its PC repeat domain as a closed toroid of two concentric α-helical rings

Structure. 2012 Mar 7;20(3):513-21. doi: 10.1016/j.str.2011.12.015.


The 26S proteasome proteolyses ubiquitylated proteins and is assembled from a 20S proteolytic core and two 19S regulatory particles (19S-RP). The 19S-RP scaffolding subunits Rpn1 and Rpn2 function to engage ubiquitin receptors. Rpn1 and Rpn2 are characterized by eleven tandem copies of a 35-40 amino acid repeat motif termed the proteasome/cyclosome (PC) repeat. Here, we reveal that the eleven PC repeats of Rpn2 form a closed toroidal structure incorporating two concentric rings of α helices encircling two axial α helices. A rod-like N-terminal domain consisting of 17 stacked α helices and a globular C-terminal domain emerge from one face of the toroid. Rpn13, an ubiquitin receptor, binds to the C-terminal 20 residues of Rpn2. Rpn1 adopts a similar conformation to Rpn2 but differs in the orientation of its rod-like N-terminal domain. These findings have implications for understanding how 19S-RPs recognize, unfold, and deliver ubiquitylated substrates to the 20S core.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Hexosyltransferases
  • Models, Molecular*
  • Molecular Sequence Data
  • Proteasome Endopeptidase Complex / chemistry*
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Conformation*
  • Sequence Alignment
  • Tandem Repeat Sequences / genetics
  • Ubiquitin / metabolism


  • Ubiquitin
  • Hexosyltransferases
  • RPN2 protein, human
  • Proteasome Endopeptidase Complex