Structure of a Blm10 complex reveals common mechanisms for proteasome binding and gate opening

Mol Cell. 2010 Mar 12;37(5):728-35. doi: 10.1016/j.molcel.2010.02.002.

Abstract

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 A 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain
  • Crystallography, X-Ray
  • Genotype
  • Mitochondria / enzymology*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Proteasome Endopeptidase Complex / chemistry*
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Binding
  • Protein Conformation
  • Reactive Oxygen Species / metabolism
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • Blm10 protein, S cerevisiae
  • Reactive Oxygen Species
  • Saccharomyces cerevisiae Proteins
  • Proteasome Endopeptidase Complex

Associated data

  • PDB/3L5Q