Bid: a Bax-like BH3 protein

Oncogene. 2008 Dec;27 Suppl 1:S93-104. doi: 10.1038/onc.2009.47.

Abstract

Bid, a pro-apoptotic member of the Bcl-2 family, was initially discovered through binding to both pro-apoptotic Bax and anti-apoptotic Bcl-2. During apoptosis, Bid can be cleaved not only by caspase-8 during death receptor apoptotic signaling, but also by other caspases, granzyme B, calpains and cathepsins. Protease-cleaved Bid migrates to mitochondria where it induces permeabilization of the outer mitochondrial membrane that is dependent on the pro-apoptotic proteins Bax and/or Bak, and thus Bid acts as a sentinel for protease-mediated death signals. Although sequence analysis suggests that Bid belongs to the BH3-only subgroup of the Bcl-2 family, structural and phylogenetic analysis suggests that Bid may be more related to multi-BH region proteins such as pro-apoptotic Bax. Analysis of membrane binding by protease-cleaved Bid reveals mechanistic similarities with the membrane binding of Bax. For both proteins, membrane binding is characterized by relief of N-terminal inhibition of sequences promoting migration to membranes, insertion into the bilayer of the central hydrophobic hairpin helices and exposure of the BH3 region. These findings implicate Bid as a BH3-only protein that is both structurally and functionally related to multi-BH region Bcl-2 family proteins such as Bax.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • BH3 Interacting Domain Death Agonist Protein / chemistry
  • BH3 Interacting Domain Death Agonist Protein / physiology*
  • Cyclin D1 / physiology
  • Humans
  • Mitochondria / physiology
  • Mitochondrial Membranes / metabolism
  • Models, Molecular
  • Peptide Hydrolases / physiology
  • Permeability
  • Phosphorylation
  • Protein Conformation
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • bcl-2-Associated X Protein / chemistry
  • bcl-2-Associated X Protein / physiology
  • bcl-Associated Death Protein / physiology

Substances

  • BAX protein, human
  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • bcl-2-Associated X Protein
  • bcl-Associated Death Protein
  • Cyclin D1
  • Peptide Hydrolases