Membrane promotes tBID interaction with BCLXL
Membrane promotes tBID interaction with BCLXL
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DOI：
10.1038/nsmb.1671
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发表时间：
2009-11-01
影响因子：
16.8
通讯作者：
Schwille, Petra
中科院分区：
文献类型：
--
作者：
Garcia-Saez, Ana J.;Ries, Jonas;Schwille, Petra
关于B细胞CLL/淋巴瘤2（BCL 2）蛋白的分子机制的两个重要问题涉及促凋亡和抗凋亡成员之间的相互作用网络以及它们在凋亡期间易位到线粒体膜的作用。我们使用荧光相关光谱来定量溶液和膜中BH 3相互作用结构域死亡激动剂（BID）及其截短形式tBID与C末端截短的B细胞淋巴瘤超大蛋白（BCLXL Delta Ct）的分子相互作用，并且我们发现（i）仅活性形式tBID结合BCLXL Delta Ct，并且（ii）膜强烈促进它们之间的结合。特别地，来自BID的BH 3肽破坏溶液中的tBID-BCLXL复合物，但仅部分破坏脂质双层中的tBID-BCLXL复合物。这些数据表明，tBID-BCLXL在溶液和脂质膜中的相互作用是不同的，并且它们支持BCLXL抑制tBID主要发生在膜上的模型。我们的研究结果意味着膜在调节BCL 2蛋白之间的相互作用中起着积极的作用，而这一作用迄今为止一直被低估。
Two important questions on the molecular mechanism of the B cell CLL/lymphoma 2 (BCL2) proteins involve the interaction network between pro-and antiapoptotic members and the role of their translocation to the mitochondrial membrane during apoptosis. We used fluorescence correlation spectroscopy to quantify the molecular interactions of BH3-interacting domain death agonist (BID) and its truncated form tBID with the B cell lymphoma extra-large protein truncated at the C terminus (BCLXL Delta Ct) in solution and in membranes, and we found that (i) only the active form tBID binds to BCLXL Delta Ct and (ii) that the membrane strongly promotes binding between them. Particularly, a BH3 peptide from BID disrupts the tBID-BCLXL complex in solution, but only partially in lipid bilayers. These data indicate that tBID-BCLXL interactions in solution and lipid membranes are distinct, and they support a model in which BCLXL inhibition of tBID takes place predominantly at the membrane. Our findings imply an active role of the membrane in modulating the interactions between BCL2 proteins that has so far been underestimated.