title: Bid: a Bax-like BH3 protein.
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.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: L P
authors.initials: LP
authors.lastname: Billen
authors.forename: A
authors.initials: A
authors.lastname: Shamas-Din
authors.forename: D W
authors.initials: DW
authors.lastname: Andrews
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000737:chemistry / Q000502:physiology*; D019938:Cyclin D1 / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000502:physiology; D051336:Mitochondrial Membranes / Q000378:metabolism; D008958:Models, Molecular; D010447:Peptide Hydrolases / Q000502:physiology; D010539:Permeability; D010766:Phosphorylation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000502:physiology; D051025:bcl-Associated Death Protein / Q000502:physiology
chemical_list: C494826:BAX protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D019938:Cyclin D1; D010447:Peptide Hydrolases