title: Membrane binding by tBid initiates an ordered series of events culminating in membrane permeabilization by Bax.
abstract: In normal circumstances, the Bcl-2 family dutifully governs when cells die. However, the rules of engagement between the pro- and antiapoptotic family members are still contested, and how Bax is transformed from a cytosolic monomer to an outer mitochondrial membrane-permeabilizing oligomer is unclear. With fluorescence techniques and an in vitro system, the combination of tBid and Bax produced dramatic membrane permeabilization. The membrane is not a passive partner in this process beause membranes are required for the protein-protein interactions to occur. Simultaneous measurements of these interactions revealed an ordered series of steps required for outer membrane permeabilization: (1) tBid rapidly binds to membranes, where (2) tBid interacts with Bax, causing (3) Bax insertion into membranes and (4) oligomerization, culminating in (5) membrane permeabilization. Bcl-XL prevents membrane-bound tBid from binding Bax. Bad releases tBid from Bcl-XL, restoring both tBid binding to Bax and membrane permeabilization.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Lovell
authors.forename: Lieven P
authors.initials: LP
authors.lastname: Billen
authors.forename: Scott
authors.initials: S
authors.lastname: Bindner
authors.forename: Aisha
authors.initials: A
authors.lastname: Shamas-Din
authors.forename: Cecile
authors.initials: C
authors.lastname: Fradin
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; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism*; D002417:Cattle; D008081:Liposomes / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D008081:Liposomes; D051028:bcl-2-Associated X Protein