On Dec 16th, 2019, Dr. Aiming Ren’s laboratory from Life Sciences Institute of Zhejiang University, in collaboration with Prof. Ronald Micura’s group from Leopold Franzens University, Austria published a research article in Nature Communications entitled “SAM-VI riboswitch structure and signature for ligand discrimination”. The structure of SAM-VI riboswitch and the ligand-dependent regulation mechanism were reported for the first time.
Riboswitches are metabolite-sensing, conserved domains located in non-coding regions of mRNA that are central to regulation of gene expression. The first three-dimensional structure of the recently discovered S-adenosyl-L-methionine responsive SAM-VI riboswitch was reported in the article, in which 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, the ligand discrimination mode of SAM-VI was revealed by additional X-ray structures of this riboswitch bound to S-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.
Dr. Aiai Sun from Aiming Ren’s group, Ms. Catherina Gasser from Ronald Micura’s group and Dr. Fudong Li from University of Science and Technology of China are co-first authors. Dr. Aiming Ren and Prof. Ronald Micura are the corresponding authors. The research was supported by grants from the Natural Science Foundation of China, the outstanding youth fund of Zhejiang Province, the Fundamental Research Funds for the Central Universities and the new faculty start-up funds from Zhejiang University.
Text link：https://www.nature.com/articles/s41467-019-13600-9
