A structural viral mimic of prosurvival Bcl-2: A pivotal role for sequestering proapoptotic Bax and Bak
A structural viral mimic of prosurvival Bcl-2: A pivotal role for sequestering proapoptotic Bax and Bak
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DOI：
10.1016/j.molcel.2007.02.004
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发表时间：
2007-03-23
期刊：
影响因子：
16
通讯作者：
Colman, Peter M.
中科院分区：
文献类型：
--
作者：
Kvansakul, Marc;van Delft, Mark F.;Colman, Peter M.
许多病毒表达抗凋亡蛋白以对抗宿主防御机制，否则宿主防御机制将触发感染细胞的快速清除。例如，腺病毒和一些γ-疱疹病毒表达促存活Bcl-2的同源物以破坏宿主的凋亡机制。粘液瘤病毒是痘科的一种双链DNA病毒，具有抗凋亡的毒力因子M11 L。其三维结构的分析表明，尽管缺乏任何一级序列的相似性Bcl-2，它采用了几乎相同的蛋白质折叠。这使得它能够与BH 3结构域，特别是Bax和巴克的结构域结合。我们发现M11 L主要通过隔离Bax和巴克起作用，从而阻断这些必需的细胞死亡介质的杀伤作用。这些发现扩展了像Bcl-2一样阻断细胞凋亡的蛋白质序列家族，并支持这些蛋白质的促生存作用关键取决于它们结合和拮抗Bax和/或巴克的能力的结论。
Many viruses express antiapoptotic proteins to counter host defense mechanisms that would otherwise trigger the rapid clearance of infected cells. For example, adenoviruses and some gamma-herpesviruses express homologs of prosurvival Bcl-2 to subvert the host's apoptotic machinery. Myxoma virus, a double-stranded DNA virus of the pox family, harbors antiapoptotic M11L, its virulence factor. Analysis of its three-dimensional structure reveals that despite lacking any primary sequence similarity to Bcl-2, it adopts a virtually identical protein fold. This allows it to associate with BH3 domains, especially those of Bax and Bak. We found that M11L acts primarily by sequestering Bax and Bak, thereby blocking the killing action of these essential cell-death mediators. These findings expand the family of protein sequences that act like Bcl-2 to block apoptosis and support the conclusion that the prosurvival action of these proteins critically depends on their ability to bind and antagonize Bax and/or Bak.