HslVU Peptidase as a Model for the Eukaryotic 26S Proteasome

On the sequence level, HslV shows sequence similarity with the yS-subunits of arch-aebacterial and eukaryotic proteasomes. The crystal structure of E. coli HslV confirmed that individual subunits share the Ntn-hydrolase fold with Thrl at the N-terminus as the nucleophile, just as in proteasomes. Despite these similarities, there are substantial differences between bacterial HslVU and archaebacterial and eukaryotic 20S proteasomes. In contrast to HslVU, 20S proteasomes are assembled from four rings of seven subunits each, that build up a central proteolytic chamber and two flanking antechambers. 

Currently, high-resolution EM image reconstructions for the 26S proteasome (Walz et al. 1998), but no atomic-resolution crystallographic data are available for any complex of 20S proteasomes with ATP-dependent activators. The expected assembly of PAN, the archaebacterial AAA(+) activator of proteasomes (Zwickl et al. 1999) into hexamers suggests a symmetry-mismatched complex in archaebacteria. 

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