The proteasome is an abundant protease that is critically important for numerous cellular pathways. Proteasomes are activated in vitro by three known classes of proteins/complexes, including Blm10/PA200. Here, we report a 3.4 Å resolution crystal structure of a proteasome-Blm10 complex, which reveals that Blm10 surrounds the proteasome entry pore in the 1.2 MDa complex to form a largely closed dome that is expected to restrict access of potential substrates. This architecture and the observation that Blm10 induces a disordered proteasome gate structure challenge the assumption that Blm10 functions as an activator of proteolysis in vivo. The Blm10 C terminus binds in the same manner as seen for 11S activators and inferred for 19S/PAN activators and indicates a unified model for gate opening. We also demonstrate that Blm10 acts to maintain mitochondrial function. Consistent with the structural data, the C-terminal residues of Blm10 are needed for this activity. © 2010 Elsevier Inc. All rights reserved.
Sadre-Bazzaz, K., Whitby, F. G., Robinson, H., Formosa, T., & Hill, C. P. (2010). Structure of a Blm10 Complex Reveals Common Mechanisms for Proteasome Binding and Gate Opening. Molecular Cell, 37(5), 728–735. https://doi.org/10.1016/j.molcel.2010.02.002