Ter-dependent stress response systems: novel pathways related to metal sensing, production of a nucleoside-like metabolite, and DNA-processing
Ter-dependent stress response systems: novel pathways related to metal sensing, production of a nucleoside-like metabolite, and DNA-processing
复制标题
DOI：
10.1039/c2mb25239b
复制
发表时间：
2012-01-01
影响因子：
--
通讯作者：
Aravind, L.
中科院分区：
文献类型：
--
作者：
Anantharaman, Vivek;Iyer, Lakshminarayan M.;Aravind, L.
细菌 ter 簇和 TelA 基因的作用模式与对亚碲酸盐和其他异生有毒化合物、成孔大肠杆菌素和几种噬菌体的天然抵抗力有关，近二十年来一直是个谜。通过比较基因组学、序列图谱搜索和结构分析，我们提供了证据，证明 ter 基因产物及其功能伙伴构成了以前未被充分认识的细菌化学应激反应和抗病毒防御系统。基于来自保守基因邻域和结构域结构的背景信息，我们表明ter基因产物和TelA位于膜连接金属识别复合物的中心，其调节分支包括磷酸化依赖性信号转导、RNA依赖性调节、核苷样代谢物的生物合成和DNA加工。我们的分析表明，多个金属结合和非结合的 TerD 旁系同源物和 TerC 可能构成膜相关复合物，其中可能还包括 TerB 和 TerY，并具有几个不同的金属结合位点。 TerB 结构域的各个版本还可能结合小分子配体，并将 TerD 旁系同源物-TerC 复合物连接到包含磷酸核糖基转移酶 (PRTase)、ATP 抓取酰胺酶、TIM 桶碳碳裂解酶和 HAD 磷酸酯酶的生物合成模块，预计这些模块可合成新型核苷样分子。其中一种 PRT 酶也可能通过其 Pelota/核糖体蛋白 L7AE 样结构域与 RNA 相互作用。冯维勒布兰德因子 A 结构域蛋白 TerY 预计是独特磷酸化开关的一部分，偶联蛋白激酶和 PP2C 磷酸酶。我们基于来自大量保守基因邻域和结构域结构的证据表明，TerB 和 TelA 结构域都与不同细菌中的不同脂质相互作用结构域（例如两个新的 PH 样结构域和 Coq4 结构域）相关，并且可能包含膜相关的感觉复合物，这些复合物可能还包含周质结合蛋白 II 和 OmpA 结构域。我们还表明，TerD 和 TerB 结构域以及 TerY 相关磷酸化系统在功能上与许多不同的 DNA 加工复合物相关，这些复合物的特征是具有 SWI2/SNF2 和 RecQ 样解旋酶的蛋白质、多个 AAA + ATP 酶、McrC-N 末端结构域蛋白、几种限制性核酸内切酶折叠 DNA 酶、DNA 结合结构域和一个 VII 型/Esx 样系统，它是预测的 DNA 转移装置的中心。预计这些 DNA 加工模块和相关基因将参与响应噬菌体的限制或自杀行为，并可能修复外源性物质引起的 DNA 损伤。在一些真核生物中，ter系统的某些成分似乎被招募来与泛素系统和钙信号通路一起发挥作用。
The mode of action of the bacterial ter cluster and TelA genes, implicated in natural resistance to tellurite and other xenobiotic toxic compounds, pore-forming colicins and several bacteriophages, has remained enigmatic for almost two decades. Using comparative genomics, sequence-profile searches and structural analysis we present evidence that the ter gene products and their functional partners constitute previously underappreciated, chemical stress response and anti-viral defense systems of bacteria. Based on contextual information from conserved gene neighborhoods and domain architectures, we show that the ter gene products and TelA lie at the center of membrane-linked metal recognition complexes with regulatory ramifications encompassing phosphorylation-dependent signal transduction, RNA-dependent regulation, biosynthesis of nucleoside-like metabolites and DNA processing. Our analysis suggests that the multiple metal-binding and non-binding TerD paralogs and TerC are likely to constitute a membrane-associated complex, which might also include TerB and TerY, and feature several, distinct metal-binding sites. Versions of the TerB domain might also bind small molecule ligands and link the TerD paralog-TerC complex to biosynthetic modules comprising phosphoribosyltransferases (PRTases), ATP grasp amidoligases, TIM-barrel carbon-carbon lyases, and HAD phosphoesterases, which are predicted to synthesize novel nucleoside-like molecules. One of the PRTases is also likely to interact with RNA by means of its Pelota/Ribosomal protein L7AE-like domain. The von Willebrand factor A domain protein, TerY, is predicted to be part of a distinct phosphorylation switch, coupling a protein kinase and a PP2C phosphatase. We show, based on the evidence from numerous conserved gene neighborhoods and domain architectures, that both the TerB and TelA domains have been linked to diverse lipid-interaction domains, such as two novel PH-like and the Coq4 domains, in different bacteria, and are likely to comprise membrane-associated sensory complexes that might additionally contain periplasmic binding-protein-II and OmpA domains. We also show that the TerD and TerB domains and the TerY-associated phosphorylation system are functionally linked to many distinct DNA-processing complexes, which feature proteins with SWI2/SNF2 and RecQ-like helicases, multiple AAA + ATPases, McrC-N-terminal domain proteins, several restriction endonuclease fold DNases, DNA-binding domains and a type-VII/Esx-like system, which is at the center of a predicted DNA transfer apparatus. These DNA-processing modules and associated genes are predicted to be involved in restriction or suicidal action in response to phages and possibly repairing xenobiotic-induced DNA damage. In some eukaryotes, certain components of the ter system appear to be recruited to function in conjunction with the ubiquitin system and calcium-signaling pathways.