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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structural basis of differential ligand recognition by two classes of bis-(3 '-5 ')-cyclic dimeric guanosine monophosphate-binding riboswitches
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Structural basis of differential ligand recognition by two classes of bis-(3 '-5 ')-cyclic dimeric guanosine monophosphate-binding riboswitches

机译：两类双-（3'-5'）-环二聚鸟苷单磷酸结合核糖开关对差异配体识别的结构基础

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摘要

The bis-(3' -5' )-cyclic dimeric guanosine monophosphate (c-di-GMP) signaling pathway regulates biofilm formation, virulence, and other processes in many bacterial species and is critical for their survival. Two classes of c-di-GMP-binding riboswitches have been discovered that bind this second messenger with high affinity and regulate diverse downstream genes, underscoring the importance of RNA receptors in this pathway. We have solved the structure of a c-di-GMP-ll riboswitch, which reveals that the ligand is bound as part of a triplex formed with a pseudoknot. The structure also shows that the guanine bases of c-di-GMP are recognized through noncanonical pairings and that the phosphodiester backbone is not contacted by the RNA. Recognition is quite different from that observed in the c-di-GMP-l riboswitch, demonstrating that at least two independent solutions for RNA second messenger binding have evolved. We exploited these differences to design a c-di-GMP analog that selectively binds the c-di-GMP-ll aptamer over the c-di-GMP-l RNA. There are several bacterial species that contain both types of riboswitches, and this approach holds promise as an important tool for targeting one riboswitch, and thus one gene, over another in a selective fashion.
机译：双-（3'-5'）-环二聚鸟苷单磷酸鸟嘌呤（c-di-GMP）信号传导途径调节许多细菌物种中生物膜的形成，毒力和其他过程，并且对其生存至关重要。已经发现了两类与c-di-GMP结合的核糖开关，它们以高亲和力结合该第二信使并调节各种下游基因，从而强调了该途径中RNA受体的重要性。我们已经解决了c-di-GMP-11核糖开关的结构，该结构揭示了配体作为假结形成的三链体的一部分被结合。该结构还表明，c-di-GMP的鸟嘌呤碱基可通过非经典配对识别，并且磷酸二酯主链不会与RNA接触。识别与在c-di-GMP-1核糖开关中观察到的识别有很大不同，这表明已经发展了至少两种独立的RNA第二信使结合溶液。我们利用这些差异来设计c-di-GMP类似物，其在c-di-GMP-1 RNA上选择性地结合c-di-GMP-11适体。有几种细菌都包含两种类型的核糖开关，这种方法有望作为一种重要工具，以一种选择性方式将一个核糖开关（一个基因）靶向另一个基因。

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    Kathryn D. Smith; Carly A. Shanahan; Emily L. Moore; Aline C. Simon; Scott A. Strobel;

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    Department of Chemistry, Yale University, New Haven, CT 06520;

    Department of Chemistry, Yale University, New Haven, CT 06520;

    Department of Molecular Biophysics and Biochemistry, Yale University,New Haven, CT 06520;

    Department of Molecular Biophysics and Biochemistry, Yale University,New Haven, CT 06520;

    Department of Chemistry, Yale University, New Haven, CT 06520,Department of Molecular Biophysics and Biochemistry, Yale University,New Haven, CT 06520;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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