Metazoan Maelstrom is an RNA-binding protein that has evolved from an ancient nuclease active in protists.

Metazoan Maelstrom is an RNA-binding protein that has evolved from an ancient nuclease active in protists.
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DOI:
10.1261/rna.049437.114
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发表时间:
2015-05
期刊:
RNA (New York, N.Y.)
影响因子:
--
通讯作者:
Pillai RS
Pillai RS
中科院分区:
其他
文献类型:
--
作者:
Chen KM;Campbell E;Pandey RR;Yang Z;McCarthy AA;Pillai RS

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Piwi相互作用RNA(piRNA)引导Piwi argonaute到它们的转座子靶点进行沉默。高度保守的蛋白Maelstrom与该途径中的皮尔纳生物发生和效应子作用相关。Maelstrom的一个定义特征是未知分子功能的预测MAEL结构域。在这里,我们提出了第一个晶体结构的MAEL域从MAEL大漩涡,揭示了核酸酶折叠。整体架构类似于在Mg 2+或Mn 2+依赖性DEDD核酸酶中发现的架构,但一个明显的区别特征是存在由保守的ECHC残基配位的结构Zn 2+离子。引人注目的是,动物界的后生动物大漩涡直系同源物缺乏催化DEDD残基,正如我们所展示的,大漩涡作为核酸酶是无活性的。然而,来自变形虫的具有两个序列基序(DEDD和ECHC)的含MAEL结构域的蛋白作为核糖核酸外切酶是稳健活性的。最后,我们表明,MAEL结构域的MAELx大漩涡显示出很强的亲和力单链RNA。我们的研究表明,古老的MAEL核酸酶结构域演变为后生动物大漩涡中的RNA结合模块。
Piwi-interacting RNAs (piRNAs) guide Piwi argonautes to their transposon targets for silencing. The highly conserved protein Maelstrom is linked to both piRNA biogenesis and effector roles in this pathway. One defining feature of Maelstrom is the predicted MAEL domain of unknown molecular function. Here, we present the first crystal structure of the MAEL domain from Bombyx Maelstrom, which reveals a nuclease fold. The overall architecture resembles that found in Mg2+- or Mn2+-dependent DEDD nucleases, but a clear distinguishing feature is the presence of a structural Zn2+ ion coordinated by the conserved ECHC residues. Strikingly, metazoan Maelstrom orthologs across the animal kingdom lack the catalytic DEDD residues, and as we show for Bombyx Maelstrom are inactive as nucleases. However, a MAEL domain-containing protein from amoeba having both sequence motifs (DEDD and ECHC) is robustly active as an exoribonuclease. Finally, we show that the MAEL domain of Bombyx Maelstrom displays a strong affinity for single-stranded RNAs. Our studies suggest that the ancient MAEL nuclease domain evolved to function as an RNA-binding module in metazoan Maelstrom.
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