SAM-VI riboswitch structure and signature for ligand discrimination
SAM-VI riboswitch structure and signature for ligand discrimination
复制标题
用于配体辨别的 SAM-VI 核糖开关结构和特征
DOI：
10.1038/s41467-019-13600-9
复制
发表时间：
2019-12-16
影响因子：
16.6
通讯作者：
Ren, Aiming
中科院分区：
文献类型：
--
作者：
Sun, Aiai;Gasser, Catherina;Ren, Aiming
Riboswitches are metabolite-sensing, conserved domains located in non-coding regions of mRNA that are central to regulation of gene expression. Here we report the first three-dimensional structure of the recently discoveredS-adenosyl-L-methionine responsive SAM-VI riboswitch. SAM-VI adopts a unique fold and ligand pocket that are distinct from all other known SAM riboswitch classes. The ligand binds to the junctional region with its adenine tightly intercalated and Hoogsteen base-paired. Furthermore, we reveal the ligand discrimination mode of SAM-VI by additional X-ray structures of this riboswitch bound toS-adenosyl-L-homocysteine and a synthetic ligand mimic, in combination with isothermal titration calorimetry and fluorescence spectroscopy to explore binding thermodynamics and kinetics. The structure is further evaluated by analysis of ligand binding to SAM-VI mutants. It thus provides a thorough basis for developing synthetic SAM cofactors for applications in chemical and synthetic RNA biology.
