Characterizing Bcl-2 Family Protein Conformation and Oligomerization Using Cross-Linking and Antibody Gel-Shift in Conjunction with Native PAGE

Methods Mol Biol. 2016:1419:185-96. doi: 10.1007/978-1-4939-3581-9_14.

Abstract

The Bcl-2 family of proteins tightly controls the intrinsic or mitochondrial pathway of apoptosis. This family is subdivided based on function into pro-survival proteins (Bcl-2, Bcl-xL, Bcl-w, Mcl-1, Bfl-1/A1) and pro-apoptotic proteins. The pro-apoptotic subset is further divided into those proteins that initiate the pathway, the BH3-only proteins (including Bim, Puma, Noxa, and Bid), and those that execute the pathway, Bak and Bax. Whether a cell lives or dies in response to apoptotic stress is determined by the interactions of the Bcl-2 family, which is in turn influenced by their conformation. We describe here a protocol to interrogate the interactions and conformation of the Bcl-2 family of proteins under native conditions.

Keywords: Apoptosis; Bak; Bcl-2; Cross-linking; Mitochondria; Native polyacrylamide gel electrophoresis; Oligomerization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / chemistry*
  • Apoptosis Regulatory Proteins / metabolism*
  • Cells, Cultured
  • Cross-Linking Reagents / metabolism*
  • Electrophoretic Mobility Shift Assay / methods*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Mice
  • Mitochondria / metabolism
  • Native Polyacrylamide Gel Electrophoresis / methods*
  • Protein Conformation
  • Proto-Oncogene Proteins c-bcl-2 / chemistry*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • Cross-Linking Reagents
  • Proto-Oncogene Proteins c-bcl-2