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A disorder-to-order transition mediates RNA-binding of the Caenorhabditis elegans protein MEX-5
Biophysical Journal ( IF 3.4 ) Pub Date : 2020-04-01 , DOI: 10.1016/j.bpj.2020.02.032
Davide Tavella 1 , Asli Ertekin 1 , Hila Schaal 1 , Sean P Ryder 1 , Francesca Massi 1
Affiliation  

CCCH-type tandem zinc finger (TZF) domains are found in many RNA-binding proteins (RBPs) that regulate the essential processes of post-transcriptional gene expression and splicing through direct protein-RNA interactions. In Caenorhabditis elegans, RBPs control the translation, stability, or localization of maternal messenger RNAs required for patterning decisions before zygotic gene activation. MEX-5 (Muscle EXcess) is a C. elegans protein that leads a cascade of RBP localization events that is essential for axis polarization and germline differentiation after fertilization. Here, we report that at room temperature, the CCCH-type TZF domain of MEX-5 contains an unstructured zinc finger that folds upon binding of its RNA target. We have characterized the structure and dynamics of the TZF domain of MEX-5 and designed a variant MEX-5 in which both fingers are fully folded in the absence of RNA. Within the thermal range experienced by C. elegans, the population of the unfolded state of the TZF domain of MEX-5 varies. We observe that the TZF domain becomes less disordered at lower temperatures and more disordered at higher temperatures. However, in the temperature range in which C. elegans is fertile, when MEX-5 needs to be functional, only one of the two zinc fingers is folded.

中文翻译:

无序到有序的转变介导秀丽隐杆线虫蛋白 MEX-5 的 RNA 结合

CCCH 型串联锌指 (TZF) 结构域存在于许多 RNA 结合蛋白 (RBP) 中,它们通过直接的蛋白质-RNA 相互作用调节转录后基因表达和剪接的基本过程。在秀丽隐杆线虫中,RBP 控制合子基因激活前模式决定所需的母体信使 RNA 的翻译、稳定性或定位。MEX-5 (Muscle EXcess) 是一种秀丽隐杆线虫蛋白,可导致一系列 RBP 定位事件,这对于受精后的轴极化和种系分化至关重要。在这里,我们报告说,在室温下,MEX-5 的 CCCH 型 TZF 结构域包含一个非结构化的锌指,该锌指在与其 RNA 靶标结合时折叠。我们已经描述了 MEX-5 的 TZF 结构域的结构和动力学,并设计了一个变体 MEX-5,其中两个手指在没有 RNA 的情况下完全折叠。在秀丽隐杆线虫经历的温度范围内,MEX-5 的 TZF 结构域的展开状态的种群变化。我们观察到 TZF 结构域在较低温度下变得不那么无序,而在较高温度下变得更加无序。然而,在秀丽隐杆线虫可繁殖的温度范围内,当 MEX-5 需要发挥作用时,只有两个锌指中的一个被折叠。
更新日期:2020-04-01
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