Ligand recognition and discrimation in the S-adenosylhomocysteine (SAH) sensing riboswitch

S-腺苷高半胱氨酸（SAH）传感核糖开关中的配体识别和区分

• 批准号: 169741400
• 负责人: Professor Dr. Jens Wöhnert
• 金额: --
• 依托单位: Institut für Molekulare Biowissenschaften
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/169741400?language=en
• 关键词: Ligand; recognition; discrimation; adenosylhomocysteine; SAH

Riboswitches have been very recently identified as a fundamentally new class of genetic control elements that modulate gene expression in bacteria, plants and fungi through direct and specific interactions between structured mRNA domains and small metabolite molecules. These mRNA domains recognize their cognate ligands with remarkably high specificity and affinity and utilize intricate three-dimensional structures to this end. Furthermore, they are able to discriminate against chemically closely related molecules. An especially remarkable example for this discrimation is found in the riboswitch groups which either bind S-adenosylmethionine (SAM) or S-adenosylhomocysteine (SAH). These two metabolites differ only by the presence or absence of a single methyl group and a positively charged sulfonium ion. Nevertheless these riboswitches bind either SAM or SAH with a 200 to > 1000fold higher affinity. Whereas for three different classes of SAM-binding riboswitches structures of the riboswitch-ligand complexes have been solved, no structural information is available for the SAH-binding riboswitch. The goal of this project is to solve the three-dimensional structure of the SAH riboswitch aptamer domain in complex with SAH in solution using NMR-spectroscopy to reveal the mode of SAH recognition and the structural basis for ligand discrimination.

最近，核糖开关被认为是一类全新的遗传控制元件，它通过结构化 mRNA 结构域和小代谢物分子之间的直接和特异性相互作用来调节细菌、植物和真菌中的基因表达。这些 mRNA 结构域以非常高的特异性和亲和力识别其同源配体，并为此利用复杂的三维结构。此外，它们能够区分化学上密切相关的分子。这种区别的一个特别显着的例子是在结合 S-腺苷甲硫氨酸 (SAM) 或 S-腺苷高半胱氨酸 (SAH) 的核糖开关基团中发现的。这两种代谢物的区别仅在于是否存在单个甲基和带正电的锍离子。然而，这些核糖开关以 200 至 > 1000 倍高的亲和力结合 SAM 或 SAH。尽管对于三类不同类别的 SAM 结合核糖开关，核糖开关-配体复合物的结构已得到解决，但尚无 SAH 结合核糖开关的结构信息。该项目的目标是利用核磁共振波谱解析溶液中与SAH复合的SAH核糖开关适体结构域的三维结构，以揭示SAH识别模式和配体辨别的结构基础。