Rax forms multispanning monomers that oligomerize to permeabilize membranes during apoptosis
Rax forms multispanning monomers that oligomerize to permeabilize membranes during apoptosis
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DOI：
10.1038/sj.emboj.7600675
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发表时间：
2005-06-15
期刊：
影响因子：
11.4
通讯作者：
Andrews, DW
中科院分区：
文献类型：
--
作者：
Annis, MG;Dlugosz, PJ;Andrews, DW
Bax通过线粒体外膜通透性促进细胞死亡，其机制尚未明确。然而，在缺乏基因c-myc的细胞中，Bax的膜通透性被线粒体中阻止Bax的变化所阻断。寡聚化。使用药物处理的c-myc空细胞和表达Myc的细胞来绘制线粒体通透化前后膜上Bax的拓扑结构。对Bax的单半胱氨酸突变体进行化学标记，发现Bax在低聚化和膜渗透之前将“孔结构域”（螺旋α 5- α 6）和尾锚（螺旋α 9）插入到膜中。在表达myc的细胞中，不需要额外的Bax拓扑变化来促进寡聚化和细胞色素c的释放。我们的研究结果表明，与大多数成孔蛋白不同，Bax膜渗透是由跨膜单体的寡聚化引起的，而不是预先形成的寡聚物的孔域的协同插入。
Bax promotes cell death by permeabilizing mitochondrial outer membranes by an unresolved mechanism. However, in cells lacking the gene c-myc, membrane permeabilization by Bax is blocked by changes in the mitochondria that prevent Bax. oligomerization. Drug-treated c-myc null cells and cells expressing Myc were used to map the topology of Bax in membranes prior to and after mitochondrial permeabilization. Chemical labeling of single cysteine mutants of Bax using a membrane bilayer impermeant cysteine-specific modifying agent revealed that Bax inserted both the 'pore domain' (helices alpha 5-alpha 6), and the tail-anchor (helix alpha 9) into membranes prior to oligomerization and membrane permeabilization. Additional topology changes for Bax were not required in Myc-expressing cells to promote oligomerization and cytochrome c release. Our results suggest that unlike most pore-forming proteins, Bax membrane permeabilization results from oligomerization of transmembrane monomers rather than concerted insertion of the pore domains of a preformed oligomer.