Two-dimensional Blue native/SDS gel electrophoresis of multi-protein complexes from whole cellular lysates: a proteomics approach

Mol Cell Proteomics. 2004 Feb;3(2):176-82. doi: 10.1074/mcp.T300010-MCP200. Epub 2003 Dec 9.

Abstract

Identification and characterization of multi-protein complexes is an important step toward an integrative view of protein-protein interaction networks that determine protein function and cell behavior. The limiting factor for identifying protein complexes is the method for their separation. Blue native PAGE (BN-PAGE) permits a high-resolution separation of multi-protein complexes under native conditions. To date, BN-PAGE has only been applicable to purified material. Here, we show that dialysis permits the analysis of multi-protein complexes of whole cellular lysates by BN-PAGE. We visualized different multi-protein complexes by immunoblotting including forms of the eukaryotic proteasome. Complex dynamics after gamma interferon stimulation of cells was studied, and an antibody shift assay was used to detect protein-protein interactions in BN-PAGE. Furthermore, we identified defined protein complexes of various proteins including the tumor suppressor p53 and c-Myc. Finally, we identified multi-protein complexes via mass spectrometry, showing that the method has a wide potential for functional proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cysteine Endopeptidases / metabolism*
  • Electrophoresis, Gel, Two-Dimensional
  • Electrophoresis, Polyacrylamide Gel
  • HeLa Cells
  • Humans
  • Interferon-gamma / metabolism*
  • Jurkat Cells
  • Mice
  • Multienzyme Complexes / metabolism*
  • Proteasome Endopeptidase Complex
  • Protein Binding
  • Proteomics*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • MYC protein, human
  • Multienzyme Complexes
  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Protein p53
  • Interferon-gamma
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex