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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structural basis for specific recognition of multiple mRNA targets by a PUF regulatory protein
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Structural basis for specific recognition of multiple mRNA targets by a PUF regulatory protein

机译:PUF调节蛋白特异性识别多个mRNA靶标的结构基础

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摘要

Caenorhabditis elegans fem-3 binding factor (FBF) is a founding member of the PUMILIO/FBF (PUF) family of mRNA regulatory proteins. It regulates multiple mRNAs critical for stem cell maintenance and germline development. Here, we report crystal structures of FBF in complex with 6 different 9-nt RNA sequences, including elements from 4 natural mRNAs. These structures reveal that FBF binds to conserved bases at positions 1-3 and 7-8. The key specificity determinant of FBF vs. other PUF proteins lies in positions 4-6. In FBF/RNA complexes, these bases stack directly with one another and turn away from the RNA-binding surface. A short region of FBF is sufficient to impart its unique specificity and lies directly opposite the flipped bases. We suggest that this region imposes a flattened curvature on the protein; hence, the requirement for the additional nucleotide. The principles of FBF/RNA recognition suggest a general mechanism by which PUF proteins recognize distinct families of RNAs yet exploit very nearly identical atomic contacts in doing so.
机译:秀丽隐杆线虫fem-3结合因子(FBF)是mRNA调控蛋白PUMILIO / FBF(PUF)家族的创始成员。它调节对干细胞维持和种系发育至关重要的多种mRNA。在这里,我们报告与6个不同的9-nt RNA序列,包括来自4个天然mRNA的元素复杂的FBF的晶体结构。这些结构揭示了FBF在位置1-3和7-8处与保守碱基结合。 FBF与其他PUF蛋白的关键特异性决定因素位于位置4-6。在FBF / RNA复合物中,这些碱基彼此直接堆叠,并远离RNA结合表面。 FBF的短区域足以赋予其独特的特异性,并直接位于翻转碱基的对面。我们建议该区域在蛋白质上施加平坦的曲率。因此,需要额外的核苷酸。 FBF / RNA识别的原理提出了一种通用机制,通过这种机制,PUF蛋白可以识别不同的RNA家族,但可以利用它们几乎完全相同的原子接触。

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