Extensive DNA mimicry by the ArdA anti-restriction protein and its role in the spread of antibiotic resistance.
Extensive DNA mimicry by the ArdA anti-restriction protein and its role in the spread of antibiotic resistance.
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DOI：
10.1093/nar/gkp478
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发表时间：
2009-08
影响因子：
14.9
通讯作者：
Dryden DT
中科院分区：
文献类型：
--
作者：
McMahon SA;Roberts GA;Johnson KA;Cooper LP;Liu H;White JH;Carter LG;Sanghvi B;Oke M;Walkinshaw MD;Blakely GW;Naismith JH;Dryden DT
在许多原核生物包括重要的致病物种中发现的ardA基因允许相关的移动的遗传元件逃避普遍存在的I型DNA限制系统，从而帮助抗性基因在细菌群体中的传播。因此，ardA是一个主要的医疗保健问题。我们已经解决了从接合转座子Tn 916的ArdA蛋白的结构，并发现它具有一个新的极其细长的弯曲的圆柱形结构与定义的螺旋槽。表面上高密度的天冬氨酸和谷氨酸残基遵循螺旋模式，整个蛋白质模拟B型DNA的42个碱基对延伸，使ArdA成为迄今为止已知的最大的DNA模拟物。该二聚体结构的每个单体包含三个α-β结构域，每个结构域具有不同的折叠。这些结构域与先前确定的具有完全不同功能的蛋白质具有相同的折叠。这种DNA模拟解释了ArdA如何结合和抑制I型限制性内切酶，我们证明了来自致病菌的6种不同的ArdA可以在大肠杆菌中发挥作用，这些大肠杆菌具有一系列不同的I型限制性内切酶系统。
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.
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影响因子：
14.9
作者：
Atanasiu, C;Su, TJ;Dryden, DTF
通讯作者：
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14.9
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Janscak, P;Dryden, DTF;Firman, K
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Richardson DC
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作者：
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通讯作者：
Phillips, Simon E. V.
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作者：
Dryden, DTF;Tock, MR
通讯作者：
Tock, MR