The structure of a Bcl-xL/Bim fragment complex:: implications for bim function
The structure of a Bcl-xL/Bim fragment complex:: implications for bim function
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DOI：
10.1016/s1074-7613(03)00234-6
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发表时间：
2003-09-01
期刊：
影响因子：
32.4
通讯作者：
Kappler, JW
中科院分区：
文献类型：
--
作者：
Liu, XQ;Dai, SD;Kappler, JW
在抗原驱动的扩增后，参与免疫应答的大多数T细胞通过依赖于Bcl-2相关蛋白Bim和Bax或巴克的凋亡而迅速死亡。这些蛋白质如何被激活和相互作用的细节仍然不清楚。小鼠Bcl-x（L）与Bim的长螺旋片段结合的晶体结构表明，Bim的结构与具有Bcl-2样折叠的蛋白质非常不同，并且可能使Bim的BH 3区域组成性暴露。基于BcI-x（L）和Bax之间的结构同源性，我们预测Bim与Bax的结合需要Bax倒数第二个α螺旋的置换。与这一预测一致，该短螺旋的截短是Bim/Bax相互作用所需的，并导致Bax的自发激活。我们的研究结果表明，Bim和Bax/巴克可能需要活化的T细胞凋亡的方式。
After antigen-driven expansion, the majority of T cells involved in an immune response die rapidly by apoptosis dependent on the Bcl-2 related proteins, Bim and Bax or Bak. The details of how these proteins are activated and interact are still unclear. The crystal structure of mouse Bcl-x(L) bound to a long helical fragment of Bim indicates that the structure of Bim is very different from proteins with a Bcl-2-like fold and may leave the BH3 region of Bim constitutively exposed. Based on the structural homology between BcI-x(L) and Bax, we predicted that binding of Bim to Bax would require displacement of the Bax penultimate alpha helix. Consistent with this prediction, truncation of this short helix was required for Bim/Bax interaction and led to spontaneous activation of Bax. Our results suggest a way in which both Bim and Bax/Bak might be required for activated T cell apoptosis.