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.
School of Biosciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK.
Hans
H
Heindl
Pamela
P
Greenwell
Noam
N
Weingarten
Tamas
T
Kiss
Gabor
G
Terstyanszky
Robert O J
RO
Weinzierl
D020134:Catalytic Domain / Q000235:genetics; D002412:Cations / Q000737:chemistry*; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D017016:Methanococcaceae / Q000201:enzymology*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D002412:Cations; D012321:DNA-Directed RNA Polymerases