Rad23 escapes degradation because it lacks a proteasome initiation region

Nat Commun. 2011 Feb 8:2:192. doi: 10.1038/ncomms1194.

Abstract

Rad23 is an adaptor protein that binds to both ubiquitinated substrates and to the proteasome. Despite its association with the proteasome, Rad23 escapes degradation. Here we show that Rad23 remains stable because it lacks an effective initiation region at which the proteasome can engage the protein and unfold it. Rad23 contains several internal, unstructured loops, but these are too short to act as initiation regions. Experiments with model proteins show that internal loops must be surprisingly long to engage the proteasome and support degradation. These length requirements are not specific to Rad23 and reflect a general property of the proteasome.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cytochromes c1 / genetics
  • DNA Primers / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Linear Models
  • Molecular Sequence Data
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Binding*
  • Protein Unfolding*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • DNA Primers
  • DNA-Binding Proteins
  • RAD23 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Cytochromes c1
  • Proteasome Endopeptidase Complex