Chou J J, Li H, Salvesen G S, Yuan J, Wagner G
Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, Massachusetts 02138, USA.
Cell. 1999 Mar 5;96(5):615-24. doi: 10.1016/s0092-8674(00)80572-3.
We report the solution structure of BID, an intracellular cross-talk agent that can amplify FAS/TNF apoptotic signal through the mitochondria death pathway after Caspase 8 cleavage. BID contains eight alpha helices where two central hydrophobic helices are surrounded by six amphipathic ones. The fold resembles poreforming bacterial toxins and shows similarity to BCL-XL although sequence homology to BCL-XL is limited to the 16-residue BH3 domain. Furthermore, we modeled a complex of BCL-XL and BID by aligning the BID and BAK BH3 motifs in the known BCL-XL-BAK BH3 complex. Additionally, we show that the overall structure of BID is preserved after cleavage by Caspase 8. We propose that BID has both BH3 domain-dependent and -independent modes of action in inducing mitochondrial damage.
我们报道了BID的溶液结构，BID是一种细胞内信号传导介质，在半胱天冬酶8切割后，可通过线粒体死亡途径放大FAS/TNF凋亡信号。BID包含八个α螺旋，其中两个中央疏水螺旋被六个两亲性螺旋包围。其折叠结构类似于形成孔道的细菌毒素，并且与BCL-XL相似，尽管与BCL-XL的序列同源性仅限于16个残基的BH3结构域。此外，我们通过在已知的BCL-XL-BAK BH3复合物中比对BID和BAK BH3基序，构建了BCL-XL和BID的复合物模型。另外，我们发现半胱天冬酶8切割后BID的整体结构得以保留。我们提出，BID在诱导线粒体损伤方面具有依赖和不依赖BH3结构域的作用模式。
