Membrane Binding by tBid Initiates an Ordered Series of Events Culminating in Membrane Permeabilization by Bax
Membrane Binding by tBid Initiates an Ordered Series of Events Culminating in Membrane Permeabilization by Bax
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DOI：
10.1016/j.cell.2008.11.010
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发表时间：
2008-12-12
期刊：
影响因子：
64.5
通讯作者：
Andrews, David W.
中科院分区：
文献类型：
--
作者：
Lovell, Jonathan F.;Billen, Lieven P.;Andrews, David W.
在正常情况下，当细胞死亡时，Bcl-2家族负责控制。然而，促凋亡和抗凋亡家族成员之间的作用规则仍然存在争议，Bax如何从细胞质单体转化为线粒体外膜渗透性低聚物尚不清楚。利用荧光技术和体外系统，tBid和Bax的结合产生了显著的膜透性。膜在这个过程中不是一个被动的伙伴，因为膜是蛋白质-蛋白质相互作用发生所必需的。同时测量这些相互作用揭示了外膜渗透所需的一系列有序步骤：(1)tBid快速结合膜，其中(2)tBid与Bax相互作用，导致(3)Bax插入膜和(4)寡聚，最终导致(5)膜渗透。Bcl-XL阻止膜结合tBid结合Bax。Bad从Bcl-XL中释放tBid，恢复tBid与Bax的结合和膜透性。
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.