Pup grows up: in vitro characterization of the degradation of pupylated proteins

Abstract

By reconstituting the recently discovered prokaryotic ubiquitin-like protein (Pup)--proteasome degradation system in vitro, Weber-Ban and colleagues (Striebel et al, 2010) elucidate its mechanism and describe a surprising variation on the established principles of protease targeting. Nevertheless, their findings suggest that the bacterial and eukaryotic systems follow the same overall principles even if the details differ.

Figure 1

Comparison of different classes of ATP-dependent proteases, shown as a side-on cross-section. (A) The eukaryotic 26S proteasome, composed of a 20S core particle (blue α and β subunits) flanked by 19S regulatory subunits (magenta and orange). The 19S subunits bind to the substrate through the covalent ubiquitin modification (yellow) and unfold it by pulling on the unstructured initiation site (bright green). Ubiquitin is removed to be recycled during the degradation process. (B) The bacterial protease ClpXP, composed of rings of the protease ClpP (dark green) and the ATPase motor ClpX (red). ClpX binds to the degradation signal, in this case the ssrA peptide sequence (green), which also serves as the site for the initiation of degradation. (C) The actinobacterial proteasome, consisting of a 20S core particle similar to that of the 26S proteasome, and a single ring of the ATPase Mpa (purple). Mpa binds to the substrate through the covalent Pup modification (light green). Pup has an N-terminal unstructured region, which serves as the site for the initiation of degradation, leading to complete degradation of Pup.