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

Journal Article · Fri Mar 12 04:00:00 EST 2010 · Molecular Cell

DOI:https://doi.org/10.1016/j.molcel.2010.02.002· OSTI ID:1014284

Sadre-Bazzaz, K; Robinson, H; Whitby, F G; Formosa, T; Hill, C P

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 {angstrom} 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.

• Research Organization: BROOKHAVEN NATIONAL LABORATORY (BNL)
• Sponsoring Organization: DOE - OFFICE OF SCIENCE
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1014284
• Report Number(s): BNL--91332-2010-JA; KP1605010
• Journal Information: Molecular Cell, Journal Name: Molecular Cell Journal Issue: 5 Vol. 37
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
73 NUCLEAR PHYSICS AND RADIATION PHYSICS
CRYSTAL STRUCTURE
IN VITRO
IN VIVO
PROTEINS
PROTEOLYSIS
RESIDUES
RESOLUTION
SUBSTRATES
UNIFIED MODEL