Abstract
SummaryRiboswitches are structural elements found in mRNA molecules that couple small-molecule binding to regulation of gene expression, usually by controlling transcription or translation. We have determined high-resolution crystal structures of the ykkC guanidine III riboswitch from Thermobifida fusca. The riboswitch forms a classic H-type pseudoknot that includes a triple helix that is continuous with a central core of conserved nucleotides. These form a left-handed helical ramp of inter-nucleotide interactions, generating the guanidinium cation binding site. The ligand is hydrogen bonded to the Hoogsteen edges of two guanine bases. The binding pocket has a side opening that can accommodate a small side chain, shown by structures with bound methylguanidine, aminoguanidine, ethylguanidine, and agmatine. Comparison of the new structure with those of the guanidine I and II riboswitches reveals that evolution generated three different structural solutions for guanidine binding and subsequent gene regulation, although with some common elements.
Highlights
Riboswitches are bacterial cis-acting genetic regulatory elements that reside in mRNA molecules (Roth and Breaker, 2009; Serganov and Nudler, 2013)
They function by binding small molecules so as to alter the local conformation, thereby switching on or off gene expression either at the transcriptional or translational level in most cases
Construction and Crystallography A 41 nt RNA corresponding to the Thermobifida fusca ykkC guanidine III riboswitch (Figure 1B) was made by chemical synthesis
Summary
Riboswitches are bacterial cis-acting genetic regulatory elements that reside in mRNA molecules (Roth and Breaker, 2009; Serganov and Nudler, 2013). They function by binding small molecules so as to alter the local conformation, thereby switching on or off gene expression either at the transcriptional or translational level in most cases. It was found that they respond to guanidine (Figure 1) (Nelson et al, 2017), which was not fully appreciated to be a metabolite in bacterial cells This compound is highly toxic, and cells must be detoxified by proteins that either convert it to less harmful species (e.g., carboxylases), or transport it out of the cell (efflux pumps). We shall in general refer to this as guanidine except where its charge is relevant
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