Molecular Basis of the Interaction between Proapoptotic Truncated BID (tBID) Protein and Mitochondrial Carrier Homologue 2 (MTCH2) Protein KEY PLAYERS IN MITOCHONDRIAL DEATH PATHWAY
Molecular Basis of the Interaction between Proapoptotic Truncated BID (tBID) Protein and Mitochondrial Carrier Homologue 2 (MTCH2) Protein KEY PLAYERS IN MITOCHONDRIAL DEATH PATHWAY
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DOI：
10.1074/jbc.m111.328377
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发表时间：
2012-04-27
影响因子：
4.8
通讯作者：
Friedler, Assaf
中科院分区：
文献类型：
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作者：
Katz, Chen;Zaltsman-Amir, Yehudit;Friedler, Assaf
线粒体载体同源物2（MTCH 2）和截短BID（tBID）之间的相互作用的分子基础的特点。这些蛋白质参与细胞凋亡途径，它们之间的相互作用可以作为抗癌先导化合物的靶点。响应于凋亡信号，MTCH 2将tBID募集到线粒体，在那里它激活凋亡。肽阵列筛选与生物化学和生物物理技术的组合被用来表征tBID和MTCH 2之间的相互作用的机制在结构和分子水平。鉴定了介导蛋白质之间相互作用的区域。蛋白质之间的两个特异性结合位点被确定为结合MTCH 2残基140 - 161的tBID残基59 - 73和结合MTCH 2残基240 - 290的tBID残基111 - 125。衍生自tBID残基111 - 125和59 - 73的肽在骨肉瘤细胞中诱导细胞死亡。这些肽可以作为抗癌药物的先导化合物，通过靶向tBID-MTCH 2相互作用发挥作用。
The molecular basis of the interaction between mitochondrial carrier homologue 2 (MTCH2) and truncated BID (tBID) was characterized. These proteins participate in the apoptotic pathway, and the interaction between them may serve as a target for anticancer lead compounds. In response to apoptotic signals, MTCH2 recruits tBID to the mitochondria, where it activates apoptosis. A combination of peptide arrays screening with biochemical and biophysical techniques was used to characterize the mechanism of the interaction between tBID and MTCH2 at the structural and molecular levels. The regions that mediate the interaction between the proteins were identified. The two specific binding sites between the proteins were determined to be tBID residues 59-73 that bind MTCH2 residues 140-161, and tBID residues 111-125 that bind MTCH2 residues 240-290. Peptides derived from tBID residues 111-125 and 59-73 induced cell death in osteosarcoma cells. These peptides may serve as lead compounds for anticancer drugs that act by targeting the tBID-MTCH2 interaction.