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-H C (bridge–helix C-terminal hinge) cause a substantial increase in specific activity (‘superactivity’). Fully atomistic molecular dynamics simulations show that kinking of the BH-H C 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.