Structure of human RNase L reveals the basis for regulated RNA decay in the IFN response.
Structure of human RNase L reveals the basis for regulated RNA decay in the IFN response.
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人RNase L的结构揭示了IFN响应中调节RNA衰减的基础。
DOI：
10.1126/science.1249845
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发表时间：
2014-03-14
期刊：
影响因子：
--
通讯作者：
Korennykh A
中科院分区：
文献类型：
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作者：
Han Y;Donovan J;Rath S;Whitney G;Chitrakar A;Korennykh A
人组织中I型干扰素（IFN）激活的标志性机制之一涉及激酶同源性核糖核酸内切酶RNase L切割细胞内RNA。我们报告2.8和2.1埃的晶体结构的人RNase L与合成和天然配体和一个片段的RNA底物的复合物。RNA酶L形成由锚蛋白（ANK）和激酶同源（KH）结构域稳定的交叉同源二聚体，其定位两个激酶延伸核酸酶（KEN）结构域用于不对称RNA识别。一个KEN原聚体识别同一核苷酸（U），而另一个原聚体在核苷酸+1和+2之间切割RNA。ANK、KH和KEN结构域的协调作用从而提供了RNA酶L对病毒和宿主RNA靶标的调节的序列特异性切割。
One of the hallmark mechanisms activated by type I interferons (IFNs) in human tissues involves cleavage of intracellular RNA by the kinase homology endoribonuclease RNase L. We report 2.8 and 2.1 angstrom crystal structures of human RNase L in complexes with synthetic and natural ligands and a fragment of an RNA substrate. RNase L forms a crossed homodimer stabilized by ankyrin (ANK) and kinase homology (KH) domains, which positions two kinase extension nuclease (KEN) domains for asymmetric RNA recognition. One KEN protomer recognizes an identity nucleotide (U), whereas the other protomer cleaves RNA between nucleotides +1 and +2. The coordinated action of the ANK, KH, and KEN domains thereby provides regulated, sequence-specific cleavage of viral and host RNA targets by RNase L.