Membrane Binding by tBid Initiates an Ordered Series of Events Culminating in Membrane Permeabilization by Bax

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 unclea...

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Veröffentlicht in:Cell 2008-12, Vol.135 (6), p.1074-1084
Hauptverfasser: Lovell, Jonathan F., Billen, Lieven P., Bindner, Scott, Shamas-Din, Aisha, Fradin, Cecile, Leber, Brian, Andrews, David W.
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container_end_page 1084
container_issue 6
container_start_page 1074
container_title Cell
container_volume 135
creator Lovell, Jonathan F.
Billen, Lieven P.
Bindner, Scott
Shamas-Din, Aisha
Fradin, Cecile
Leber, Brian
Andrews, David W.
description 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.
doi_str_mv 10.1016/j.cell.2008.11.010
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source MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
subjects Animals
Apoptosis
bcl-2-Associated X Protein - metabolism
BH3 Interacting Domain Death Agonist Protein - metabolism
Cattle
CELLBIO
Liposomes - metabolism
Mitochondrial Membranes - metabolism
SIGNALING
title Membrane Binding by tBid Initiates an Ordered Series of Events Culminating in Membrane Permeabilization by Bax
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