Extensive DNA mimicry by the ArdA anti-restriction protein and its role in the spread of antibiotic resistance.
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 alpha-beta 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
Stephen A
SA
Centre for Biomolecular Science, The University, St Andrews KY16 9ST, UK.
Roberts
Gareth A
GA
Johnson
Kenneth A
KA
Cooper
Laurie P
LP
Liu
Huanting
H
White
John H
JH
Carter
Lester G
LG
Sanghvi
Bansi
B
Oke
Muse
M
Walkinshaw
Malcolm D
MD
Blakely
Garry W
GW
Naismith
James H
JH
Dryden
David T F
DT
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D015280:DNA Restriction-Modification Enzymes / Q000037:antagonists & inhibitors*; D015253:Deoxyribonucleases, Type I Site-Specific / Q000037:antagonists & inhibitors; D019281:Dimerization; D024881:Drug Resistance, Bacterial / Q000235:genetics; D016680:Genome, Bacterial; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000737:chemistry
D001426:Bacterial Proteins; D015280:DNA Restriction-Modification Enzymes; D004247:DNA; C093244:DNA modification methylase EcoKI; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D015253:Deoxyribonucleases, Type I Site-Specific