Structural Superimposition

Abstact

The dynamic interplay between RNA structure and its associated Mg(2+) ions is central to RNA function yet remains poorly understood at a near-atomic level(1-4). Here, using a heterogeneity-focused protocol for cryo-electron microscopy data analysis of conformationally flexible RNA particles, we determined the structures of RNase P RNA ensembles composed of 76 coexisting active and inactive conformers that differ in a transient tertiary interaction that is critical for activity. The binding of the accessory protein does not change the local structure but induces thermodynamic allostery that enhances catalysis by altering the dynamics of the tertiary interaction. Four distinct classes of Mg(2+) ions have critical roles in the structure, dynamics and catalysis of the conformational ensembles. Together, these findings establish a new paradigm in which catalysis is regulated through multimodal communications coupled with the dynamics of RNA-Mg(2+) conformational ensembles, rather than a single static catalytic structure in a single action mode.