The Architecture of the Anbu Complex Reflects an Evolutionary Intermediate at the Origin of the Proteasome System

Structure. 2017 Jun 6;25(6):834-845.e5. doi: 10.1016/j.str.2017.04.005. Epub 2017 May 4.

Abstract

Proteasomes are self-compartmentalizing proteases that function at the core of the cellular protein degradation machinery in eukaryotes, archaea, and some bacteria. Although their evolutionary history is under debate, it is thought to be linked to that of the bacterial protease HslV and the hypothetical bacterial protease Anbu (ancestral beta subunit). Here, together with an extensive bioinformatic analysis, we present the first biophysical characterization of Anbu. Anbu forms a dodecameric complex with a unique architecture that was only accessible through the combination of X-ray crystallography and small-angle X-ray scattering. While forming continuous helices in crystals and electron microscopy preparations, refinement of sections from the crystal structure against the scattering data revealed a helical open-ring structure in solution, contrasting the ring-shaped structures of proteasome and HslV. Based on this primordial architecture and exhaustive sequence comparisons, we propose that Anbu represents an ancestral precursor at the origin of self-compartmentalization.

Keywords: Anbu; SAXS; proteasome; protein evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Catalytic Domain
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Evolution, Molecular*
  • Models, Molecular
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Conformation
  • Protein Multimerization
  • Scattering, Small Angle
  • X-Ray Diffraction

Substances

  • Bacterial Proteins
  • Proteasome Endopeptidase Complex