How Bacterial Chemoreceptors Evolve Novel Ligand Specificities
How Bacterial Chemoreceptors Evolve Novel Ligand Specificities
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DOI：
10.1128/mbio.03066-19
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发表时间：
2020-01-01
期刊：
影响因子：
6.4
通讯作者：
Krell, Tino
中科院分区：
文献类型：
--
作者：
Antonio Gavira, Jose;Gumerov, Vadim M.;Krell, Tino
化学受体信号通路是细菌信号转导的主要方式之一，铜绿假单胞菌PAO 1是研究其功能的重要模型。在该菌株的26种化学感受器中，PctA具有广泛的配体范围并且响应于大多数蛋白质氨基酸，而PctB和PctC具有窄得多的范围并且分别显示出对L-谷氨酰胺和γ-氨基丁酸的强配体偏好。使用几种比较基因组学方法，我们表明，这些受体是旁系同源：pctA基因复制的共同祖先的属假单胞菌导致pctC，而pctB起源于另一个，独立的pctA复制的共同祖先的铜绿假单胞菌。因此，广泛的氨基酸化学感受器是进化上的老，和化学感受器，补充“失踪”的氨基酸传感能力出现后，在特定的假单胞菌谱系。使用比较序列分析，新解决的晶体结构的PctA，PctB和PctC配体结合域，和他们的分子动力学模拟，我们确定了一个保守的氨基酸识别基序和变化的配体结合口袋，导致新的配体特异性。此外，我们确定了驱动这组化学感受器进化的主要力量。重要信息许多细菌拥有大量的化学感受器，它们识别各种不同的化合物。在这项研究中分析的基因组中，超过60%含有旁系同源化学感受器，这表明它们以高频率出现。我们提供了第一次了解旁系同源受体如何演变，并表明两个化学受体与一个狭窄的配体范围已经从一个祖先的蛋白质与广泛的化学效应谱。蛋白质结构表明，在配体结合位点的多重变化占在配体光谱的差异。这项工作奠定了基础，旨在建立配体结合进化的原则，在这里报告是否可以推广到更广泛的细菌中的感觉蛋白的进一步研究。
Chemoreceptor-based signaling pathways are among the major modes of bacterial signal transduction, and Pseudomonas aeruginosa PAO1 is an important model to study their function. Of the 26 chemoreceptors of this strain, PctA has a broad ligand range and responds to most of the proteinogenic amino acids, whereas PctB and PctC have a much narrower range and show strong ligand preference for L-glutamine and gamma-aminobutyrate, respectively. Using several comparative genomics approaches, we show that these receptors are paralogs: pctA gene duplication in the common ancestor of the genus Pseudomonas led to pctC, whereas pctB originated through another, independent pctA duplication in the common ancestor of P. aeruginosa. Thus, the broad-range amino acid chemoreceptor was evolutionarily older, and chemoreceptors that complemented "missing" amino acid sensing abilities arose later in specific Pseudomonas lineages. Using comparative sequence analysis, newly solved crystal structures of PctA, PctB, and PctC ligand-binding domains, and their molecular dynamics simulations, we identified a conserved amino acid recognition motif and changes in the ligand-binding pocket that led to novel ligand specificities. In addition, we determined major forces driving the evolution of this group of chemoreceptors.IMPORTANCE Many bacteria possess a large number of chemoreceptors that recognize a variety of different compounds. More than 60% of the genomes analyzed in this study contain paralogous chemoreceptors, suggesting that they emerge with high frequency. We provide first insight on how paralogous receptors have evolved and show that two chemoreceptors with a narrow ligand range have evolved from an ancestral protein with a broad chemoeffector spectrum. Protein structures show that multiple changes in the ligand-binding site account for the differences in the ligand spectrum. This work lays the ground for further studies aimed at establishing whether the principles of ligand-binding evolution reported here can be generalized for a wider spectrum of sensory proteins in bacteria.