Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes
Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes
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DOI：
10.1073/pnas.1612322114
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发表时间：
2017-01-10
影响因子：
11.1
通讯作者：
Orzaez, Mar
中科院分区：
文献类型：
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作者：
Andreu-Fernandez, Vicente;Sancho, Monica;Orzaez, Mar
Bcl-2（B 细胞淋巴瘤 2）蛋白 Bax（Bcl-2 相关 X，凋亡调节因子）可通过线粒体外膜透化作用使细胞凋亡。健康细胞中的 Bax 活性由促存活 Bcl-2 蛋白控制。最近，C 端 Bax 跨膜结构域相互作用与 Bax 孔的形成有关。在这里，我们表明，在没有细胞凋亡刺激的情况下，Bax、Bcl-xL（超大 B 细胞淋巴瘤）和 Bcl-2 的分离跨膜结构域可以介导 Bax 与膜内促存活蛋白之间的相互作用。 Bcl-2 蛋白跨膜结构域在细菌和线粒体膜中特异性地同源寡聚和异源寡聚。它们的相互作用参与 Bcl-2 蛋白的调节，从而调节细胞凋亡活性。我们的结果表明，Bax 跨膜结构域和抗凋亡 Bcl-2 蛋白之间的相互作用代表了以前未被认识到的凋亡调节水平。
The Bcl-2 (B-cell lymphoma 2) protein Bax (Bcl-2 associated X, apoptosis regulator) can commit cells to apoptosis via outer mitochondrial membrane permeabilization. Bax activity is controlled in healthy cells by prosurvival Bcl-2 proteins. C-terminal Bax transmembrane domain interactions were implicated recently in Bax pore formation. Here, we show that the isolated transmembrane domains of Bax, Bcl-xL (B-cell lymphoma-extra large), and Bcl-2 can mediate interactions between Bax and prosurvival proteins inside the membrane in the absence of apoptotic stimuli. Bcl-2 protein transmembrane domains specifically homooligomerize and heterooligomerize in bacterial and mitochondrial membranes. Their interactions participate in the regulation of Bcl-2 proteins, thus modulating apoptotic activity. Our results suggest that interactions between the transmembrane domains of Bax and antiapoptotic Bcl-2 proteins represent a previously unappreciated level of apoptosis regulation.