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Cell. 2008 Dec 12;135(6):1074-84. doi: 10.1016/j.cell.2008.11.010.

Membrane binding by tBid initiates an ordered series of events culminating in membrane permeabilization by Bax.

Author information

1
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.

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.

PMID:
19062087
DOI:
10.1016/j.cell.2008.11.010
[Indexed for MEDLINE]
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