Sandbox Reserved 1576

Overview

Riboswitches are metabolite-sensing-mRNAs that interact with small ligands and direct expression of the genes involved in their metabolism. Riboswitches contain sensing "aptamer" modules, which create ligand-induced structural changes, that allow for controlling gene expression. They form tuning-fork structures, where the prongs go through hairpin loop interactions, and the internal bubble zips up to form an adenine binding pocket. The bound purines are held by hydrogen bonds. The encapsulated adenine is paired to cytosine through Watson-Crick base pairing. (1)

Structure

The adenine bound A-riboswitch complex uses a tuning fork-like compact fold, where stem P1 forms the handle of the tuning fork, and stems P2 and P3, which form the prongs, are aligned parallel to each other and anchored at the tips through extensive interaction between their hairpin loops L2 and L3. The central internal bubble zippers up through stacked base triple alignments between the three junction-connecting segments, J1-2, J2-3, and J3-1, and two junctional base pairs of stem P1, creating an adenine-sensing pocket within the resulting core segment of the RNA scaffold. ^[1]

The structure includes five (colored pink) and a bound (colored yellow). Four of the Mg cations are located inside of the grooves and involved in the junction-connecting segments in the fold. The remaining Mg cation is on the surface and is involved in packing interactions. The four Mg cations on the inside of the complex are surrounding the bound adenine. (1)

Function

Riboswitches are used as a form of genetic control in some bacteria, where they modulate the expression of transport and metabolic proteins. The adenine and guanine riboswitches form nearly identical binding pockets since they are both purines. The single nucleotide in the core forms a Watson-Crick base pair with its ligand. The structure of the adenine riboswitch bound to its ligand creates RNA's ability to use A-minor motifs and base tetrads, which causes the folding required to create the binding pockets. This provides the infrastructure for targeting and discrimination between similar metabolites. (1)