6lax
the mutant SAM-VI riboswitch (U6C) bound to SAM
Structural highlights
FunctionSNRPA_HUMAN Binds stem loop II of U1 snRNA. It is the first snRNP to interact with pre-mRNA. This interaction is required for the subsequent binding of U2 snRNP and the U4/U6/U5 tri-snRNP. In a snRNP-free form (SF-A) may be involved in coupled pre-mRNA splicing and polyadenylation process. Binds preferentially to the 5'-UGCAC-3' motif in vitro.[1] Publication Abstract from PubMedRiboswitches 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. SAM-VI riboswitch structure and signature for ligand discrimination.,Sun A, Gasser C, Li F, Chen H, Mair S, Krasheninina O, Micura R, Ren A Nat Commun. 2019 Dec 16;10(1):5728. doi: 10.1038/s41467-019-13600-9. PMID:31844059[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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