Molecular basis of tRNA recognition by the Elongator complex
Molecular basis of tRNA recognition by the Elongator complex
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DOI：
10.1126/sciadv.aaw2326
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发表时间：
2019-07-01
期刊：
影响因子：
13.6
通讯作者：
Glatt, Sebastian
中科院分区：
文献类型：
--
作者：
Dauden, Maria, I;Jaciuk, Marcin;Glatt, Sebastian
高度保守的延长子复合物修饰转移RNA（tRNA）的摆动碱基位置，从而调节蛋白质合成并确保蛋白质组稳定性。tRNA识别及其修饰反应的精确机制仍然难以捉摸。在这里，我们显示了低温电子显微镜结构的催化子复合物的延伸和它的tRNA结合状态的分辨率为3.3和4.4埃。这些结构解析了催化位点的细节，包括底物tRNA、铁硫簇和SAM分子，这些都通过体外和体内突变分析进行了验证。tRNA结合诱导构象重排，其将靶向反密码子碱基精确定位在活性位点。我们的研究结果为Elongator的底物识别提供了分子基础，这对于了解其在神经退行性疾病和癌症中的细胞功能和作用至关重要。
The highly conserved Elongator complex modifies transfer RNAs (tRNAs) in their wobble base position, thereby regulating protein synthesis and ensuring proteome stability. The precise mechanisms of tRNA recognition and its modification reaction remain elusive. Here, we show cryo-electron microscopy structures of the catalytic subcomplex of Elongator and its tRNA-bound state at resolutions of 3.3 and 4.4 angstrom. The structures resolve details of the catalytic site, including the substrate tRNA, the iron-sulfur cluster, and a SAM molecule, which are all validated by mutational analyses in vitro and in vivo. tRNA binding induces conformational rearrangements, which precisely position the targeted anticodon base in the active site. Our results provide the molecular basis for substrate recognition of Elongator, essential to understand its cellular function and role in neurodegenerative diseases and cancer.