Solution structure of the proapoptotic molecule BID: A structural basis for apoptotic agonists and antagonists
Solution structure of the proapoptotic molecule BID: A structural basis for apoptotic agonists and antagonists
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DOI：
10.1016/s0092-8674(00)80573-5
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发表时间：
1999-03-05
期刊：
影响因子：
64.5
通讯作者：
Cowburn, D
中科院分区：
文献类型：
--
作者：
McDonnell, JM;Fushman, D;Cowburn, D
BCL 2蛋白家族的成员是程序性细胞死亡的关键调节因子，充当凋亡激动剂或拮抗剂。在这里，我们描述了BID的溶液结构，呈现了促细胞凋亡BCL 2家族成员的结构。BCL 2家族成员的序列/结构的分析使我们能够定义一个结构超家族，这对调节促凋亡活性的一般机制有影响。对于BCL 2家族中的促凋亡功能，似乎必须满足两个标准：分子靶向细胞内膜和暴露BH 3死亡结构域。BID的活性受胱天蛋白酶8介导的切割事件调节，暴露BH 3结构域并显著改变表面电荷和疏水性，导致细胞定位的变化。
Members of the BCL2 family of proteins are key regulators of programmed cell death, acting either as apoptotic agonists or antagonists. Here we describe the solution structure of BID, presenting the structure of a proapoptotic BCL2 family member. An analysis of sequence/structure of BCL2 family members allows us to define a structural superfamily, which has implications for general mechanisms for regulating proapoptotic activity. It appears two criteria must be met for proapoptotic function within the BCL2 family: targeting of molecules to intracellular membranes, and exposure of the BH3 death domain. BID's activity is regulated by a Caspase 8-mediated cleavage event, exposing the BH3 domain and significantly changing the surface charge and hydrophobicity, resulting in a change of cellular localization.