Magnesium ions mediate ligand binding and conformational transition of the SAM/SAH riboswitch

The SAM/SAH riboswitch binds S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) with similar affinities. Mg2+ is generally known to stabilize RNA structures by neutralizing phosphates, but how it contributes to ligand binding and conformational transition is understudied. Here, extensive molecular dynamics simulations (totaling 120 & mu;s) predicted over 10 inner-shell Mg2+ ions in the SAM/SAH riboswitch. Six of them line the two sides of a groove to widen it and thereby pre-organize the riboswitch for ligand entry. They also form outer-shell coordination with the ligands and stabilize an RNA-ligand hydrogen bond, which effectively diminishes the selectivity between SAM and SAH. One Mg2+ ion unique to the apo form maintains the Shine-Dalgarno sequence in an autonomous mode and thereby facilitates its release for ribosome binding. Mg2+ thus plays vital roles in SAM/SAH riboswitch function. Molecular dynamics simulations reveal site-specific mechanisms of Mg2+ ions in conformational transitions of the SAM/SAH riboswitch for ligand and ribosome binding.