Structural Insights Into the Regulatory Particle of the Proteasome From Methanocaldococcus Jannaschii

Mol Cell. 2009 May 14;34(4):473-84. doi: 10.1016/j.molcel.2009.04.021.

Abstract

Eukaryotic proteasome consists of a core particle (CP), which degrades unfolded protein, and a regulatory particle (RP), which is responsible for recognition, ATP-dependent unfolding, and translocation of polyubiquitinated substrate protein. In the archaea Methanocaldococcus jannaschii, the RP is a homohexameric complex of proteasome-activating nucleotidase (PAN). Here, we report the crystal structures of essential elements of the archaeal proteasome: the CP, the ATPase domain of PAN, and a distal subcomplex that is likely the first to encounter substrate. The distal subcomplex contains a coiled-coil segment and an OB-fold domain, both of which appear to be conserved in the eukaryotic proteasome. The OB domains of PAN form a hexameric ring with a 13 A pore, which likely constitutes the outermost constriction of the substrate translocation channel. These studies reveal structural codes and architecture of the complete proteasome, identify potential substrate-binding sites, and uncover unexpected asymmetry in the RP of archaea and eukaryotes.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Methanococcales / enzymology*
  • Methanococcales / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Proteasome Endopeptidase Complex / chemistry*
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Conformation*
  • Protein Folding
  • Protein Subunits / chemistry*
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Sequence Alignment

Substances

  • Archaeal Proteins
  • Protein Subunits
  • Proteasome Endopeptidase Complex
  • Adenosine Triphosphatases
  • PAN enzyme

Associated data

  • PDB/3H43
  • PDB/3H4M
  • PDB/3H4P