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Analysis of a preQ1-I riboswitch in effector-free and bound states reveals a metabolite-programmed nucleobase-stacking spine that controls gene regulation.
Nucleic Acids Research ( IF 16.6 ) Pub Date : 2020-06-29 , DOI: 10.1093/nar/gkaa546
Griffin M Schroeder 1, 2 , Debapratim Dutta 1, 2 , Chapin E Cavender 1, 2 , Jermaine L Jenkins 1, 2 , Elizabeth M Pritchett 3 , Cameron D Baker 3 , John M Ashton 3 , David H Mathews 1, 2 , Joseph E Wedekind 1, 2
Affiliation  

Riboswitches are structured RNA motifs that recognize metabolites to alter the conformations of downstream sequences, leading to gene regulation. To investigate this molecular framework, we determined crystal structures of a preQ1-I riboswitch in effector-free and bound states at 2.00 Å and 2.65 Å-resolution. Both pseudoknots exhibited the elusive L2 loop, which displayed distinct conformations. Conversely, the Shine-Dalgarno sequence (SDS) in the S2 helix of each structure remained unbroken. The expectation that the effector-free state should expose the SDS prompted us to conduct solution experiments to delineate environmental changes to specific nucleobases in response to preQ1. We then used nudged elastic band computational methods to derive conformational-change pathways linking the crystallographically-determined effector-free and bound-state structures. Pathways featured: (i) unstacking and unpairing of L2 and S2 nucleobases without preQ1—exposing the SDS for translation and (ii) stacking and pairing L2 and S2 nucleobases with preQ1—sequestering the SDS. Our results reveal how preQ1 binding reorganizes L2 into a nucleobase-stacking spine that sequesters the SDS, linking effector recognition to biological function. The generality of stacking spines as conduits for effector-dependent, interdomain communication is discussed in light of their existence in adenine riboswitches, as well as the turnip yellow mosaic virus ribosome sensor.

中文翻译:


对处于无效应子和结合状态的 preQ1-I 核糖开关的分析揭示了控制基因调控的代谢物编程的核碱基堆积脊柱。



核糖开关是结构化 RNA 基序,可识别代谢物以改变下游序列的构象,从而导致基因调控。为了研究这个分子框架,我们以 2.00 Å 和 2.65 Å 分辨率确定了 preQ 1 -I 核糖开关在无效应子和束缚态下的晶体结构。两个假结都表现出难以捉摸的 L2 环,显示出不同的构象。相反,每个结构的 S2 螺旋中的 Shine-Dalgarno 序列 (SDS) 保持完整。无效应状态应暴露 SDS 的期望促使我们进行溶液实验,以描绘响应 preQ 1 的特定核碱基的环境变化。然后,我们使用微动弹性带计算方法来推导出连接晶体学确定的无效应器和束缚态结构的构象变化路径。途径特征:(i) 在没有 preQ 1 的情况下对 L2 和 S2 核碱基进行解堆积和解配对 — 暴露 SDS 进行翻译;(ii) 使用 preQ 1将 L2 和 S2 核碱基堆积和配对 — 隔离 SDS。我们的结果揭示了 preQ 1结合如何将 L2 重组为隔离 SDS 的核碱基堆积脊柱,从而将效应器识别与生物功能联系起来。根据腺嘌呤核糖开关以及萝卜黄花叶病毒核糖体传感器中的存在,讨论了堆叠棘作为效应器依赖性域间通信管道的普遍性。
更新日期:2020-08-18
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