The above structural information provides insights into the mechanism of translational regulation by the TPP riboswitch. In the apo state, the base of the L5 stem loop is disordered allowing it to interact with the downstream regulatory element (blue) through complementary base pairing. This interaction causes a rearrangement of the regulatory element structure making the Shine-Dalgarno sequence (SD, orange) accessible for the ribosome to initiate translation. The stable conformation of the thiamine sensing stem in the apo state likely promotes the formation of this L5 stem loop/regulatory element interaction. In the bound state, the equilibrium is shifted to the compacted state with an ordered L5 stem loop, which prohibits the interaction of the L5 stem loop with the regulatory element. This ultimately leads to a loss in ribosome initiation and translation.
