Docking of the proteasomal ATPases' carboxyl termini in the 20S proteasome's alpha ring opens the gate for substrate entry

Mol Cell. 2007 Sep 7;27(5):731-44. doi: 10.1016/j.molcel.2007.06.033.


The 20S proteasome functions in protein degradation in eukaryotes together with the 19S ATPases or in archaea with the homologous PAN ATPase complex. These ATPases contain a conserved C-terminal hydrophobic-tyrosine-X motif (HbYX). We show that these residues are essential for PAN to associate with the 20S and open its gated channel for substrate entry. Upon ATP binding, these C-terminal residues bind to pockets between the 20S's alpha subunits. Seven-residue or longer peptides from PAN's C terminus containing the HbYX motif also bind to these sites and induce gate opening in the 20S. Gate opening could be induced by C-terminal peptides from the 19S ATPase subunits, Rpt2, and Rpt5, but not by ones from PA28/26, which lack the HbYX motif and cause gate opening by distinct mechanisms. C-terminal residues in the 19S ATPases were also shown to be critical for gating and stability of 26S proteasomes. Thus, the C termini of the proteasomal ATPases function like a "key in a lock" to induce gate opening and allow substrate entry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / metabolism
  • Amino Acid Motifs
  • Binding Sites
  • Models, Molecular
  • Molecular Sequence Data
  • Proteasome Endopeptidase Complex / chemistry*
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Endopeptidase Complex / physiology
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Alignment


  • Saccharomyces cerevisiae Proteins
  • Proteasome Endopeptidase Complex
  • Adenosine Triphosphatases
  • PAN enzyme