Convergent evolution involving dimeric and trimeric dUTPases in pathogenicity island mobilization.
Convergent evolution involving dimeric and trimeric dUTPases in pathogenicity island mobilization.
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DOI：
10.1371/journal.ppat.1006581
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发表时间：
2017-09
期刊：
影响因子：
6.7
通讯作者：
Marina A
中科院分区：
文献类型：
--
作者：
Donderis J;Bowring J;Maiques E;Ciges-Tomas JR;Alite C;Mehmedov I;Tormo-Mas MA;Penadés JR;Marina A
dutp酶（Dut）由几乎所有的自由生物和一些病毒编码，它可以防止尿嘧啶与DNA的错误结合。我们之前提出三聚体Duts是参与不同细胞过程的调节蛋白；包括噬菌体介导的金黄色葡萄球菌致病岛SaPIbov1的转移。最近，研究表明，由噬菌体ϕNM1编码的结构无关的二聚体Dut同样能够调动SaPIbov1，这表明二聚体Duts也可能是调节蛋白。如何做到这一点仍未得到解决。在这里，我们利用体内、生化和结构方法，深入研究了二聚体Duts诱导SaPIbov1周期的信号机制。正如报道的三聚体Duts，二聚体Duts包含一个极其可变的区域，这里称为结构域VI，它参与这些酶的调节能力。值得注意的是，我们的研究结果还表明，二聚体Dut信号传导机制是由dUTP调节的，就像三聚体Dut一样。总的来说，我们的研究结果表明，尽管二聚体和三聚体Duts在序列和结构上都不相关，但它们通过类似的机制控制SaPI的转移，这是趋同进化的一个有趣例子。这种保守的作用模式突出了Duts作为调控分子的生物学意义。了解细菌水平基因转移对于确定毒素和抗生素抗性基因如何传播至关重要。噬菌体和致病性岛构成了更广泛的水平转移图的关键组成部分。SaPI是临床相关的致病性岛屿，在SaPI主抑制因子Stl的控制下，被动地驻留在宿主染色体上。我们最近描述了三聚体噬菌体编码的dutp酶（Dut）通过与相同的编码Stl相互作用，作为SaPIs子集的抗抑制物。一些金黄色葡萄球菌噬菌体编码二聚体而不是三聚体Duts，它们在序列和结构水平上完全不相关。最近的研究涉及金黄色葡萄球菌噬菌体的二聚体Dut在SaPIbov1的动员中，这也是由三聚体Duts诱导的，表明SaPIbov1的诱导机制类似。在这里，我们对SaPIbov1诱导的分析揭示了存在几种二聚体Dut的等位基因形式，具有不同的SaPI去抑制能力。一个去抑制二聚体Dut的三维结构显示了这些酶的简化版本，与任何先前表征的二聚体Dut相比，具有功能特殊性。值得注意的是，对于不相关的蛋白质，我们的研究结果表明二聚体和三聚体Duts使用的去抑制机制在概念上是相同的，包括dUTP作为第二个信使关闭Stl-Dut相互作用。我们的发现显示了Duts作为信号分子的重要性，代表了一个引人入胜的趋同进化的例子。
The dUTPase (Dut) enzymes, encoded by almost all free-living organisms and some viruses, prevent the misincorporation of uracil into DNA. We previously proposed that trimeric Duts are regulatory proteins involved in different cellular processes; including the phage-mediated transfer of the Staphylococcus aureus pathogenicity island SaPIbov1. Recently, it has been shown that the structurally unrelated dimeric Dut encoded by phage ϕNM1 is similarly able to mobilize SaPIbov1, suggesting dimeric Duts could also be regulatory proteins. How this is accomplished remains unsolved. Here, using in vivo, biochemical and structural approaches, we provide insights into the signaling mechanism used by the dimeric Duts to induce the SaPIbov1 cycle. As reported for the trimeric Duts, dimeric Duts contain an extremely variable region, here named domain VI, which is involved in the regulatory capacity of these enzymes. Remarkably, our results also show that the dimeric Dut signaling mechanism is modulated by dUTP, as with the trimeric Duts. Overall, our results demonstrate that although unrelated both in sequence and structure, dimeric and trimeric Duts control SaPI transfer by analogous mechanisms, representing a fascinating example of convergent evolution. This conserved mode of action highlights the biological significance of Duts as regulatory molecules. Understanding bacterial horizontal gene transfer is vital for establishing how toxins and antibiotic resistance genes are disseminated. Bacteriophage and pathogenicity islands make up key components of the wider horizontal transfer map. SaPIs are clinically relevant pathogenicity islands, residing passively in the host chromosome under control of the SaPI master repressor, Stl. We have recently described that the trimeric phage-encoded dUTPases (Dut) act as anti-repressors for a subset of SaPIs, by interacting with an identical encoded Stl. Some Staphylococcus aureus phages encode dimeric instead of trimeric Duts, which are completely unrelated at both sequence and structural levels. Recent work involved the dimeric Dut from S. aureus phage ϕNM1 in the mobilization of SaPIbov1, which is also induced by trimeric Duts, suggesting a similar mechanism of SaPIbov1 induction. Here, our analysis of SaPIbov1 induction reveals the existence of several allelic forms of dimeric Dut, with varying capacity for SaPI de-repression. The three-dimensional structure of one de-repressing dimeric Dut shows a simplified version of these enzymes, with functional particularities compared to any previously characterised dimeric Dut. Remarkably for unrelated proteins, our results indicate the de-repression mechanism used by dimeric and trimeric Duts is conceptually identical, involving dUTP as a second messenger turning off Stl-Dut interaction. Our findings show the significance of Duts as signalling molecules, representing a fascinating example convergent evolution in action.
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影响因子：
5.2
作者：
Kerepesi C;Szabó JE;Papp-Kádár V;Dobay O;Szabó D;Grolmusz V;Vértessy BG
通讯作者：
Vértessy BG
影响因子：
5.6
作者：
Hill, Rosanne L. L.;Dokland, Terje
通讯作者：
Dokland, Terje
DOI：
10.1107/s0907444999002085
发表时间：
1999-05-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Luft, JR;DeTitta, GT
通讯作者：
DeTitta, GT
DOI：
10.1073/pnas.1013872108
发表时间：
2011-08-30
影响因子：
11.1
作者：
Pecsi, Ildiko;Szabo, Judit E.;Toth, Judit
通讯作者：
Toth, Judit
DOI：
10.1007/978-1-61779-821-4_5
发表时间：
2012-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Arndt, Claudia;Koristka, Stefanie;Bachmann, Michael
通讯作者：
Bachmann, Michael