Proteasome Subunit Selective Activity-Based Probes Report on Proteasome Core Particle Composition in a Native Polyacrylamide Gel Electrophoresis Fluorescence-Resonance Energy Transfer Assay

J Am Chem Soc. 2016 Aug 10;138(31):9874-80. doi: 10.1021/jacs.6b04207. Epub 2016 Jul 26.

Abstract

Most mammalian tissues contain a single proteasome species: constitutive proteasomes. Tissues able to express, next to the constitutive proteasome catalytic activities (β1c, β2c, β5c), the three homologous activities, β1i, β2i and β5i, may contain numerous distinct proteasome particles: immunoproteasomes (composed of β1i, β2i and β5i) and mixed proteasomes containing a mix of these activities. This work describes the development of new subunit-selective activity-based probes and their use in an activity-based protein profiling assay that allows the detection of various proteasome particles. Tissue extracts are treated with subunit-specific probes bearing distinct fluorophores and subunit-specific inhibitors. The samples are resolved by native polyacrylamide gel electrophoresis, after which fluorescence-resonance energy transfer (FRET) reports on the nature of proteasomes present.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Catalysis
  • Cytoplasm / metabolism
  • Fluorescence Resonance Energy Transfer*
  • Fluorescent Dyes / chemistry
  • HeLa Cells
  • Humans
  • Native Polyacrylamide Gel Electrophoresis*
  • Proteasome Endopeptidase Complex / chemistry*
  • Proteasome Inhibitors / pharmacology
  • Protein Structure, Secondary

Substances

  • Fluorescent Dyes
  • Proteasome Inhibitors
  • Proteasome Endopeptidase Complex