Evolutionary genomics reveals conserved structural determinants of signaling and adaptation in microbial chemoreceptors
Evolutionary genomics reveals conserved structural determinants of signaling and adaptation in microbial chemoreceptors
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DOI：
10.1073/pnas.0609359104
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发表时间：
2007-02-20
影响因子：
11.1
通讯作者：
Zhulin, Igor B.
中科院分区：
文献类型：
--
作者：
Alexander, Roger P.;Zhulin, Igor B.
作为跨膜信号传导的重要模型，甲基接受趋化蛋白（MCP）已通过遗传、生化和结构技术得到广泛研究。然而，信号传导分子机制的细节仍不清楚。数百个物种的基因组信息的可用性使得能够识别蛋白质序列中的特征，这些特征在较长的进化距离中是保守的，因此对于功能至关重要。我们对 MCP 信号传导和适应结构域家族进行了大规模的比较基因组分析，并确定了对受体结构和功能至关重要的特征。基于结构域长度和序列保守性，我们确定了七个主要的 MCP 类别和细胞质结构域内的三个不同的结构区域：信号传导、甲基化和柔性束子结构域。以前在 MCP 中未识别的柔性束子域是一个保守元件，似乎对信号转导很重要。值得注意的是，尽管总结构域长度有 24 个到 64 个 7-aa 七联体，但细胞质结构域的 N 端和 C 端螺旋臂在长度上保持对称性并记录。在一些 MCP 中观察到对称性丧失，并伴随着感觉模块的特定变化。每个主要的 MCP 类别都有一个独特的预测甲基化位点模式，这得到了实验数据的充分支持。我们的研究结果表明，MCP 胞质结构域内的信号传导和适应功能紧密耦合，并且它们的共同进化导致了不同生物体之间趋化机制的显着多样性。
As an important model for transmembrane signaling, methyl-accepting chemotaxis proteins (MCPs) have been extensively studied by using genetic, biochemical, and structural techniques. However, details of the molecular mechanism of signaling are still not well understood. The availability of genomic information for hundreds of species enables the identification of features in protein sequences that are conserved over long evolutionary distances and thus are critically important for function. We carried out a large-scale comparative genomic analysis of the MCP signaling and adaptation domain family and identified features that appear to be critical for receptor structure and function. Based on domain length and sequence conservation, we identified seven major MCP classes and three distinct structural regions within the cytoplasmic domain: signaling, methylation, and flexible bundle subdomains. The flexible bundle subdomain, not previously recognized in MCPs, is a conserved element that appears to be important for signal transduction. Remarkably, the N- and C-terminal helical arms of the cytoplasmic domain maintain symmetry in length and register despite dramatic variation, from 24 to 64 7-aa heptads in overall domain length. Loss of symmetry is observed in some MCPs, where it is concomitant with specific changes in the sensory module. Each major MCP class has a distinct pattern of predicted methylation sites that is well supported by experimental data. Our findings indicate that signaling and adaptation functions within the MCP cytoplasmic domain are tightly coupled, and that their coevolution has contributed to the significant diversity in chemotaxis mechanisms among different organisms.