Molecular Cell
Volume 37, Issue 5, 12 March 2010, Pages 728-735
Journal home page for Molecular Cell

Short Article
Structure of a Blm10 Complex Reveals Common Mechanisms for Proteasome Binding and Gate Opening

https://doi.org/10.1016/j.molcel.2010.02.002Get rights and content
Under an Elsevier user license
open archive

Summary

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.

Highlights

► Blm10 forms a dome over the proteasome pore that may exclude protein substrates ► A disordered pore further indicates that Blm10 might not be an activator in vivo ► A common model of binding and gate opening is suggested for Blm10, 11S, and PAN/19S ► Proteasome binding by the C terminus of Blm10 acts to maintain mitochondrial function

PROTEINS

Cited by (0)