Sequence- and species-dependence of proteasomal processivity

ACS Chem Biol. 2012 Aug 17;7(8):1444-53. doi: 10.1021/cb3001155. Epub 2012 Jun 28.

Abstract

The proteasome is the degradation machine at the center of the ubiquitin-proteasome system and controls the concentrations of many proteins in eukaryotes. It is highly processive so that substrates are degraded completely into small peptides, avoiding the formation of potentially toxic fragments. Nonetheless, some proteins are incompletely degraded, indicating the existence of factors that influence proteasomal processivity. We have quantified proteasomal processivity and determined the underlying rates of substrate degradation and release. We find that processivity increases with species complexity over a 5-fold range between yeast and mammalian proteasome, and the effect is due to slower but more persistent degradation by proteasomes from more complex organisms. A sequence stretch that has been implicated in causing incomplete degradation, the glycine-rich region of the NFκB subunit p105, reduces the proteasome's ability to unfold its substrate, and polyglutamine repeats such as found in Huntington's disease reduce the processivity of the proteasome in a length-dependent manner.

Publication types

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

MeSH terms

  • Animals
  • Escherichia coli / metabolism
  • Glycine / chemistry
  • Humans
  • Hydrolysis
  • Kinetics
  • Models, Biological
  • NF-kappa B / metabolism
  • Peptides / chemistry
  • Proteasome Endopeptidase Complex / chemistry*
  • Protein Denaturation
  • Protein Folding
  • Rabbits
  • Species Specificity

Substances

  • NF-kappa B
  • Peptides
  • polyglutamine
  • Proteasome Endopeptidase Complex
  • Glycine