聚A的分子基础 RNP架构和Pan2-Pan3死亡酶的识别
Ingmar B Schäfer1, Masami Yamashita1, Jan Michael Schuller1
1Department of Structural Cell Biology, MPI of Biochemistry, Munich, Germany.
Cell
|May 21, 2019
概括
多A结合蛋白 (PABPC1/Pab1) 通过与Pan2-Pan3死亡酶复合体相互作用来调节mRNA的稳定性. 结构分析揭示了多甲尾的Pab1寡合体如何决定mRNA死亡化率.
科学领域:
- 分子生物学
- 结构生物学
- 生物化学
背景情况:
- 细胞mRNA的稳定性是由一个涉及多甲结合蛋白 (PABPC1/Pab1) 的核糖核蛋白 (RNP) 复合体控制的.
- 这种多A) RNP复合物保护mRNA免受降解,并激活Pan2-Pan3死亡酶以缩短多A尾部.
研究的目的:
- 阐明Pan2-Pan3死酶复合物与多ARNA相互作用并降解的机制.
- 通过Pab1寡合体来确定聚甲尾长度调节的结构基础.
主要方法:
- 在实验室中使用重组蛋白质复合聚甲和Pan2-Pan3死酶复合物的复合.
- 电子显微镜 (cryo-EM) 来确定复合物的结构.
- 生物化学测试以分析死亡酶活性.
主要成果:
- Pan2-Pan3 死亡酶与含有至少两种Pab1分子的多甲基RNA结合并降解.
- 冷-EM结构揭示了Pab1的寡合化接口是如何被Pan2-Pan3识别的,将多元ARNA线索到活性位点.
- 该结构解释了在细胞质mRNA的3'端观察到的周期结构.
结论:
- 聚甲尾上的Pab1寡合体作为分子统治者,控制死亡化速率.
- 这种机制提供了对mRNA多A尾长在整个mRNA的寿命中是如何调节的机制的洞察.
- 这些发现揭示了mRNA衰变调节的结构基础.
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