The Bax carboxy-terminal hydrophobic helix does not determine organelle-specific targeting but is essential for maintaining Bax in an inactive state and for stable mitochondrial membrane insertion.
The Bax carboxy-terminal hydrophobic helix does not determine organelle-specific targeting but is essential for maintaining Bax in an inactive state and for stable mitochondrial membrane insertion.
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Bax 羧基末端疏水螺旋并不决定细胞器特异性靶向，但对于维持 Bax 处于非活性状态和稳定的线粒体膜插入至关重要。
DOI：
10.1007/s10495-009-0410-2
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Wattenberg,BinksW
中科院分区：
文献类型：
--
作者：
Brock,StephanieE;Li,Chi;Wattenberg,BinksW
在这里，我们讨论促凋亡蛋白Bax的疏水羧基末端尾部的功能。尾部被塞进Bax闭合/非活性构象中的疏水口袋中。凋亡刺激改变Bax构象，暴露线粒体靶向信号。我们证实单独的Bax尾部可以特异性地靶向并锚定线粒体的客运蛋白。令人惊讶的是，我们确定Bax尾部在Bax线粒体易位中并不起主要靶向作用。突变Bax尾部以产生er靶向信号对Bax线粒体靶向没有影响。此外，我们证明了Bax尾部对Bax激活具有负调控作用。突变破坏了尾部与疏水口袋的相互作用，导致构成激活和线粒体靶向。Bax尾部的缺失也导致Bax的活性构象，然而，线粒体靶向性被取消。因此，Bax尾是线粒体易位所必需的。通过产生不能插入膜的突变尾，我们确定Bax尾部的插入是Bax线粒体靶向所必需的。我们的数据支持一个模型，即Bax尾部必须从口袋中释放出来才能激活Bax，然后在初始寻址步骤后作为锚点将Bax稳定在线粒体膜上。
Here we address the function of the hydrophobic carboxy-terminal tail of the pro-apoptotic protein Bax. The tail is tucked into a hydrophobic pocket within the closed/inactive conformation of Bax. Apoptotic stimulation changes the Bax conformation, exposing a mitochondrial-targeting signal. We confirmed that the Bax tail alone can specifically target and anchor a passenger protein to the mitochondria. Surprisingly, we determined that the Bax tail does not play the primary targeting role in Bax mitochondrial translocation. Mutating the Bax tail to produce an ER-targeting signal had no effect on Bax mitochondrial targeting. Additionally, we demonstrated that the Bax tail has a negative regulatory effect on Bax activation. Mutations that disrupt the tail interactions with the hydrophobic pocket resulted in constitutive activation and mitochondrial targeting. Deletion of the Bax tail also resulted in an active conformation of Bax, however, mitochondrial targeting was abolished. Thus, the Bax tail is required for mitochondrial translocation. By generating a mutant-tail that cannot insert into membrane, we determined that insertion of the Bax tail is required for Bax mitochondrial targeting. Our data support a model whereby the Bax tail must be released from the pocket for activation of Bax, then functions as an anchor to stabilize Bax at the mitochondrial membrane after the initial addressing step.
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影响因子：
64.8
作者：
TRAVERS, AA;BURGESS, RR
通讯作者：
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影响因子：
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通讯作者：
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DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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