Extensive DNA mimicry by the ArdA anti-restriction protein and its role in the spread of antibiotic resistance
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The ardA gene, found in many prokaryotes including important pathogenic species, allows associated mobile genetic elements to evade the ubiquitous Type I DNA restriction systems and thereby assist the spread of resistance genes in bacterial populations. As such, ardA contributes to a major healthcare problem. We have solved the structure of the ArdA protein from the conjugative transposon Tn916 and find that it has a novel extremely elongated curved cylindrical structure with defined helical grooves. The high density of aspartate and glutamate residues on the surface follow a helical pattern and the whole protein mimics a 42-base pair stretch of B-form DNA making ArdA by far the largest DNA mimic known. Each monomer of this dimeric structure comprises three alphabeta domains, each with a different fold. These domains have the same fold as previously determined proteins possessing entirely different functions. This DNA mimicry explains how ArdA can bind and inhibit the Type I restriction enzymes and we demonstrate that 6 different ardA from pathogenic bacteria can function in Escherichia coli hosting a range of different Type I restriction systems.
McMahon , S A , Roberts , G A , Johnson , K A , Cooper , L P , Liu , H , White , J H , Carter , L G , Sanghvi , B , Oke , M , Walkinshaw , M D , Blakely , G W , Naismith , J H & Dryden , D T F 2009 , ' Extensive DNA mimicry by the ArdA anti-restriction protein and its role in the spread of antibiotic resistance ' , Nucleic Acids Research , vol. 37 , no. 15 , pp. 4887-4897 . https://doi.org/10.1093/nar/gkp478
Nucleic Acids Research
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