McDonnell J M, Fushman D, Milliman C L, Korsmeyer S J, Cowburn D
Rockefeller University, New York, New York 10021, USA.
Cell. 1999 Mar 5;96(5):625-34. doi: 10.1016/s0092-8674(00)80573-5.
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.
BCL2 蛋白家族成员是程序性细胞死亡的关键调节因子，可作为凋亡激动剂或拮抗剂发挥作用。在此，我们描述了 BID 的溶液结构，展示了一个促凋亡 BCL2 家族成员的结构。对 BCL2 家族成员的序列/结构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具有启示意义。BCL2 家族内的促凋亡功能似乎必须满足两个标准：分子靶向细胞内膜，以及暴露 BH3 死亡结构域。BID 的活性受半胱天冬酶 8 介导的切割事件调节，暴露 BH3 结构域并显著改变表面电荷和疏水性，导致细胞定位发生变化。
