6LAX

the mutant SAM-VI riboswitch (U6C) bound to SAM

Summary for 6LAX

• Entry DOI: 10.2210/pdb6lax/pdb
• Descriptor: RNA (55-MER), U1 small nuclear ribonucleoprotein A, S-ADENOSYLMETHIONINE, ... (4 entities in total)
• Functional Keywords: riboswitch, sam, sam-vi, rna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 69220.78

Authors

Sun, A.,Ren, A. (deposition date: 2019-11-13, release date: 2020-01-01, Last modification date: 2024-10-23)

Primary citation

Sun, A.,Gasser, C.,Li, F.,Chen, H.,Mair, S.,Krasheninina, O.,Micura, R.,Ren, A.
SAM-VI riboswitch structure and signature for ligand discrimination.
Nat Commun, 10:5728-5728, 2019

PubMed 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.

PubMed: 31844059
DOI: 10.1038/s41467-019-13600-9

Experimental method

X-RAY DIFFRACTION (2.7 Å)