Department of Biochemistry and Biomedical Sciences and M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
Microbiol Mol Biol Rev. 2013 Sep;77(3):440-75. doi: 10.1128/MMBR.00018-13.
The most common prokaryotic signal transduction mechanisms are the one-component systems in which a single polypeptide contains both a sensory domain and a DNA-binding domain. Among the >20 classes of one-component systems, the TetR family of regulators (TFRs) are widely associated with antibiotic resistance and the regulation of genes encoding small-molecule exporters. However, TFRs play a much broader role, controlling genes involved in metabolism, antibiotic production, quorum sensing, and many other aspects of prokaryotic physiology. There are several well-established model systems for understanding these important proteins, and structural studies have begun to unveil the mechanisms by which they bind DNA and recognize small-molecule ligands. The sequences for more than 200,000 TFRs are available in the public databases, and genomics studies are identifying their target genes. Three-dimensional structures have been solved for close to 200 TFRs. Comparison of these structures reveals a common overall architecture of nine conserved α helices. The most important open question concerning TFR biology is the nature and diversity of their ligands and how these relate to the biochemical processes under their control.
最常见的原核信号转导机制是单组分系统，其中单一多肽包含感觉域和 DNA 结合域。在超过 20 类单组分系统中，TetR 家族调节剂（TFRs）广泛与抗生素抗性和编码小分子外排泵基因的调控有关。然而，TFRs 发挥着更广泛的作用，控制着涉及代谢、抗生素生产、群体感应和原核生理学许多其他方面的基因。有几个成熟的模型系统可用于研究这些重要的蛋白质，结构研究已开始揭示它们结合 DNA 和识别小分子配体的机制。在公共数据库中可获得超过 200,000 个 TFR 的序列，基因组学研究正在确定它们的靶基因。已经解决了近 200 个 TFR 的三维结构。对这些结构的比较揭示了九个保守α螺旋的常见整体结构。关于 TFR 生物学的最重要的开放性问题是它们的配体的性质和多样性，以及这些配体如何与其所控制的生化过程相关。
