Helix-7 在 Argonaute2 中为 microRNA 种子区域形成提供结构，从而实现快速的靶标识别。
Helix-7 in Argonaute2 shapes the microRNA seed region for rapid target recognition.
机构信息
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Department of BioNanoScience, Kavli Institute of NanoScience, Delft University of Technology, Delft, The Netherlands.
出版信息
EMBO J. 2018 Jan 4;37(1):75-88. doi: 10.15252/embj.201796474. Epub 2017 Sep 22.
Argonaute proteins use microRNAs (miRNAs) to identify mRNAs targeted for post-transcriptional repression. Biochemical assays have demonstrated that Argonaute functions by modulating the binding properties of its miRNA guide so that pairing to the seed region is exquisitely fast and accurate. However, the mechanisms used by Argonaute to reshape the binding properties of its small RNA guide remain poorly understood. Here, we identify a structural element, α-helix-7, in human Argonaute2 (Ago2) that is required for speed and fidelity in binding target RNAs. Biochemical, structural, and single-molecule data indicate that helix-7 acts as a molecular wedge that pivots to enforce rapid making and breaking of miRNA:target base pairs in the 3' half of the seed region. These activities allow Ago2 to rapidly dismiss off-targets and dynamically search for seed-matched sites at a rate approaching the limit of diffusion.
Argonaute 蛋白利用 microRNAs（miRNAs）来识别靶 mRNA 以进行转录后抑制。生化分析表明，Argonaute 通过调节其 miRNA 指导的结合特性来发挥作用，从而使与种子区域的配对极其快速和准确。然而，Argonaute 用于重塑其小 RNA 指导的结合特性的机制仍知之甚少。在这里，我们鉴定了人类 Argonaute2（Ago2）中的一个结构元件，α-螺旋-7，它是结合靶 RNA 时速度和保真度所必需的。生化、结构和单分子数据表明，螺旋-7 充当分子楔子，枢转而强制在种子区域的 3' 半部分快速形成和打破 miRNA:靶碱基对。这些活性使 Ago2 能够快速排除非靶标，并以接近扩散极限的速度动态搜索与种子匹配的位点。
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