SAM-VI riboswitch structure and signature for ligand discrimination

Aiai Sun, Catherina Gasser, Fudong Li, Hao Chen, Stefan Mair, Olga Krasheninina, Ronald Micura () and Aiming Ren ()
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Aiai Sun: Life Sciences Institute, Zhejiang University
Catherina Gasser: Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck, Leopold Franzens University
Fudong Li: National Science Center for Physical Sciences at Microscale Division of Molecular & Cell Biophysics and School of Life Sciences, University of Science and Technology of China
Hao Chen: Life Sciences Institute, Zhejiang University
Stefan Mair: Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck, Leopold Franzens University
Olga Krasheninina: Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck, Leopold Franzens University
Ronald Micura: Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck, Leopold Franzens University
Aiming Ren: Life Sciences Institute, Zhejiang University

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract 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 discovered S-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 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.

Date: 2019
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DOI: 10.1038/s41467-019-13600-9

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