title: During apoptosis bcl-2 changes membrane topology at both the endoplasmic reticulum and mitochondria.
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.affiliation: Department of Biochemistry, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Kim
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Annis
authors.forename: Paulina J
authors.initials: PJ
authors.lastname: Dlugosz
authors.forename: Brian
authors.initials: B
authors.lastname: Leber
authors.forename: David W
authors.initials: DW
authors.lastname: Andrews
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D008563:Membrane Lipids / Q000737:chemistry; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000494:pharmacology; D017433:Protein Structure, Secondary / Q000187:drug effects / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism*; D051381:Rats
chemical_list: D008563:Membrane Lipids; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D003545:Cysteine