Ion channel activity of the BH3 only Bcl-2 family member, BID

J Biol Chem. 1999 Jul 30;274(31):21932-6. doi: 10.1074/jbc.274.31.21932.

Abstract

BID is a member of the BH3-only subgroup of Bcl-2 family proteins that displays pro-apoptotic activity. The NH(2)-terminal region of BID contains a caspase-8 (Casp-8) cleavage site and the cleaved form of BID translocates to mitochondrial membranes where it is a potent inducer of cytochrome c release. Secondary structure and fold predictions suggest that BID has a high degree of alpha-helical content and structural similarity to Bcl-X(L), which itself is highly similar to bacterial pore-forming toxins. Moreover, circular dichroism analysis confirmed a high alpha-helical content of BID. Amino-terminal truncated BIDDelta1-55, mimicking the Casp-8-cleaved molecule, formed channels in planar bilayers at neutral pH and in liposomes at acidic pH. In contrast, full-length BID displayed channel activity only at nonphysiological pH 4.0 (but not at neutral pH) in planar bilayers and failed to form channels in liposomes even under acidic conditions. On a single channel level, BIDDelta1-55 channels were voltage-gated and exhibited multiconductance behavior at neutral pH. When full-length BID was cleaved by Casp-8, it too demonstrated channel activity similar to that seen with BIDDelta1-55. Thus, BID appears to share structural and functional similarity with other Bcl-2 family proteins known to have channel-forming activity, but its activity exhibits a novel form of activation: proteolytic cleavage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • BH3 Interacting Domain Death Agonist Protein
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism
  • Chlorides / metabolism
  • Circular Dichroism
  • Cloning, Molecular
  • Genes, bcl-2
  • Ion Channels*
  • Lipid Bilayers
  • Liposomes
  • Mice
  • Models, Molecular
  • Protein Folding
  • Protein Structure, Secondary
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-bcl-2 / chemistry
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • bcl-X Protein

Substances

  • BH3 Interacting Domain Death Agonist Protein
  • Bcl2l1 protein, mouse
  • Bid protein, mouse
  • Carrier Proteins
  • Chlorides
  • Ion Channels
  • Lipid Bilayers
  • Liposomes
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • bcl-X Protein
  • Casp8 protein, mouse
  • Casp9 protein, mouse
  • Caspase 8
  • Caspase 9
  • Caspases