Cation-π interactions induce kinking of a molecular hinge in the RNA polymerase bridge-helix domain.

RNAPs (RNA polymerases) are complex molecular machines that contain a highly conserved catalytic site surrounded by conformationally flexible domains. High-throughput mutagenesis in the archaeal model system Methanocaldococcus jannaschii has demonstrated that the nanomechanical properties of one of these domains, the bridge-helix, exert a key regulatory role on the rate of the NAC (nucleotide-addition cycle). Mutations that increase the probability and/or half-life of kink formation in the BH-HC (bridge-helix C-terminal hinge) cause a substantial increase in specific activity ('superactivity'). Fully atomistic molecular dynamics simulations show that kinking of the BH-HC appears to be driven by cation-π interactions and involve amino acid side chains that are exceptionally highly conserved in all prokaryotic and eukaryotic species.