Crystal structure and ligand-induced folding of the SAM/SAH riboswitch

Nucleic Acids Research
Lin HuangDavid M J Lilley

Abstract

While most SAM riboswitches strongly discriminate between SAM and SAH, the SAM/SAH riboswitch responds to both ligands with similar apparent affinities. We have determined crystal structures of the SAM/SAH riboswitch bound to SAH, SAM and other variant ligands at high resolution. The riboswitch forms an H-type pseudoknot structure with coaxial alignment of the stem-loop helix (P1) and the pseudoknot helix (PK). An additional three base pairs form at the non-open end of P1, and the ligand is bound at the interface between the P1 extension and the PK helix. The adenine nucleobase is stacked into the helix and forms a trans Hoogsteen-Watson-Crick base pair with a uridine, thus becoming an integral part of the helical structure. The majority of the specific interactions are formed with the adenosine. The methionine or homocysteine chain lies in the groove making a single hydrogen bond, and there is no discrimination between the sulfonium of SAM or the thioether of SAH. Single-molecule FRET analysis reveals that the riboswitch exists in two distinct conformations, and that addition of SAM or SAH shifts the population into a stable state that likely corresponds to the form observed in the crystal. A model for translational regulation...Continue Reading

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Datasets Mentioned

BETA
RF01727

Methods Mentioned

BETA
NMR
FRET
electrophoresis
co-crystallization
isothermal titration calorimetry
X-ray

Software Mentioned

PDB
phenix
REDO
PHENIX suite
PHASER
AutoSol
MOLPROBITY
Coot
MicroCal Origin
Jalview

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