During Apoptosis Bcl-2 Changes Membrane Topology at Both the Endoplasmic Reticulum and Mitochondria Academic Article uri icon

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abstract

  • In healthy cells the antiapoptotic protein Bcl-2 adopts a topology typical of tail-anchored proteins with only the hydrophobic carboxyl terminus inserted into the membrane, as shown by labeling cell lysates with a membrane-impermeant sulfhydryl-specific reagent. Induction of apoptosis in cells triggered a change in the conformation of Bcl-2 such that cysteine 158 near the base of helix 5 inserted into the lipid bilayer of both endoplasmic reticulum and mitochondria where it was protected from labeling. Addition of a peptide corresponding to the BH3 domain of the proapoptotic protein Bim to cell lysates triggered a similar conformational change in Bcl-2, demonstrating that preexisting, membrane-bound Bcl-2 proteins change topology.

authors

  • Kim, Peter K
  • Annis, Matthew G
  • Dlugosz, Paulina J
  • Leber, Brian
  • Andrews, David W

publication date

  • May 2004