Bax dimerizes via a symmetric BH3:groove interface during apoptosis
Bax dimerizes via a symmetric BH3:groove interface during apoptosis
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DOI：
10.1038/cdd.2011.138
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发表时间：
2012-04-01
影响因子：
12.4
通讯作者：
Kluck, R. M.
中科院分区：
文献类型：
--
作者：
Dewson, G.;Ma, S.;Kluck, R. M.
在细胞凋亡过程中，Bax 和 Bak 会改变构象并发生同源寡聚化，从而使线粒体透化。我们最近报道，Bak 通过 BH3 结构域和疏水表面凹槽之间的相互作用实现同二聚化，这种 BH3：凹槽相互作用是对称的，并且对称二聚体可以通过 α 6 螺旋连接形成被认为负责孔形成的高阶寡聚物。我们现在表明，在细胞和线粒体部分中的凋亡信号传导后，Bax 还通过 BH3: 凹槽相互作用形成二聚体。 BH3：Bax 的凹槽二聚体与二聚体是对称的，但更高阶的寡聚体不能通过位于 BH3 和凹槽中的半胱氨酸残基连接。 BH3：凹槽相互作用在凋亡信号传导后在大多数线粒体 Bax 中很明显，并且与细胞色素 c 释放密切相关，支持其在 Bax 功能中的核心作用。半胱氨酸连接研究暗示了 Bax α 6 螺旋之间的第二个界面，并且可以将二聚体连接到更高阶的寡聚体。我们还发现，在细胞凋亡过程中通过 BH3：凹槽相互作用形成了一批 Bax：Bak 异二聚体，进一步证明 Bax 和 Bak 通过类似的机制寡聚。这些发现强调了 BH3：凹槽相互作用在 Bcl-2 蛋白家族凋亡调节中的重要性。细胞死亡与分化 (2012) 19, 661-670; doi：10.1038/cdd.2011.138； 2011 年 10 月 21 日在线发布
During apoptotic cell death, Bax and Bak change conformation and homo-oligomerize to permeabilize mitochondria. We recently reported that Bak homodimerizes via an interaction between the BH3 domain and hydrophobic surface groove, that this BH3:groove interaction is symmetric, and that symmetric dimers can be linked via the alpha 6-helices to form the high order oligomers thought responsible for pore formation. We now show that Bax also dimerizes via a BH3:groove interaction after apoptotic signaling in cells and in mitochondrial fractions. BH3:groove dimers of Bax were symmetric as dimers but not higher order oligomers could be linked by cysteine residues placed in both the BH3 and groove. The BH3:groove interaction was evident in the majority of mitochondrial Bax after apoptotic signaling, and correlated strongly with cytochrome c release, supporting its central role in Bax function. A second interface between the Bax alpha 6-helices was implicated by cysteine linkage studies, and could link dimers to higher order oligomers. We also found that a population of Bax: Bak heterodimers generated during apoptosis formed via a BH3:groove interaction, further demonstrating that Bax and Bak oligomerize via similar mechanisms. These findings highlight the importance of BH3:groove interactions in apoptosis regulation by the Bcl-2 protein family. Cell Death and Differentiation (2012) 19, 661-670; doi:10.1038/cdd.2011.138; published online 21 October 2011