The P(II)-NAGK-PipX-NtcA Regulatory Axis of Cyanobacteria: A Tale of Changing Partners, Allosteric Effectors and Non-covalent Interactions.
The P(II)-NAGK-PipX-NtcA Regulatory Axis of Cyanobacteria: A Tale of Changing Partners, Allosteric Effectors and Non-covalent Interactions.
复制标题
DOI：
10.3389/fmolb.2018.00091
复制
发表时间：
2018
影响因子：
5
通讯作者：
Rubio V
中科院分区：
文献类型：
--
作者：
Forcada-Nadal A;Llácer JL;Contreras A;Marco-Marín C;Rubio V
PII是一种同源三聚体的非常古老且高度分布(细菌、古生菌、植物)的关键传感器-转导蛋白，它传递碳、能量和可用氮丰富或贫乏的信号，将这些信号转化为通道、酶或基因表达的活性变化。PII的感知是由PII变构效应分子三磷酸腺苷、二磷酸腺苷(在某些生物中是AMP)、2-氧戊二酸(2OG；它反映了碳的丰富和氮的缺乏)以及在许多植物中的L-谷氨酰胺介导的。蓝藻对于阐明PII功能和调控的结构基础至关重要。他们是这次审查的主题，因为收集到的信息提供了一个基于结构的PII监管网络的整体观点。对这些生物的研究产生了PII与一种酶(N-乙酰-L-谷氨酸激酶，NAGK)复合体的第一个结构，破译了PII是如何引起酶激活的，以及它是如何促进蓝藻和植物中以精氨酸形式储存的氮的。他们还揭示了PII控制基因表达的第一个明确的机制。一种小的适配蛋白PipX在氮丰富时被PII隔离，在氮缺乏时释放，通过与2OG激活的转录调节因子NTCA结合，共同激活它来交换伴侣。PII-NAGK、PII-PipX、PIPX的结构，NTCA的非活性形式和2OG激活形式，以及NTCA-2OG-PipX复合体的结构，从结构上解释了PII的调节功能，揭示了PII的T环的形状和相互作用取决于伴侣和与PII结合的变构效应。蓝藻研究也表明，在PII-PipX复合体中，管道X结合了一个额外的转录因子PLMA，从而可能扩大了管道X的作用，超越了NTCA的依赖。对这些作用的进一步探索揭示了PipX与PipY的功能相互作用，PipY是一种参与PLP动态平衡的吡哆醛-磷酸(PLP)蛋白，其在人类同源基因中的突变导致癫痫。了解这个PII-PipX调控网络不同组成部分的细胞水平和一些复合体的Kd值为在高氮丰度和低氮丰度下对系统进行总体建模提供了基本背景。蓝藻网络可以指导在其他生物体中寻找类似的成分，特别是在PipX功能类似物中。
PII, a homotrimeric very ancient and highly widespread (bacteria, archaea, plants) key sensor-transducer protein, conveys signals of abundance or poorness of carbon, energy and usable nitrogen, converting these signals into changes in the activities of channels, enzymes, or of gene expression. PII sensing is mediated by the PII allosteric effectors ATP, ADP (and, in some organisms, AMP), 2-oxoglutarate (2OG; it reflects carbon abundance and nitrogen scarcity) and, in many plants, L-glutamine. Cyanobacteria have been crucial for clarification of the structural bases of PII function and regulation. They are the subject of this review because the information gathered on them provides an overall structure-based view of a PII regulatory network. Studies on these organisms yielded a first structure of a PII complex with an enzyme, (N-acetyl-Lglutamate kinase, NAGK), deciphering how PII can cause enzyme activation, and how it promotes nitrogen stockpiling as arginine in cyanobacteria and plants. They have also revealed the first clear-cut mechanism by which PII can control gene expression. A small adaptor protein, PipX, is sequestered by PII when nitrogen is abundant and is released when is scarce, swapping partner by binding to the 2OG-activated transcriptional regulator NtcA, co-activating it. The structures of PII-NAGK, PII-PipX, PipX alone, of NtcA in inactive and 2OG-activated forms and as NtcA-2OG-PipX complex, explain structurally PII regulatory functions and reveal the changing shapes and interactions of the T-loops of PII depending on the partner and on the allosteric effectors bound to PII. Cyanobacterial studies have also revealed that in the PII-PipX complex PipX binds an additional transcriptional factor, PlmA, thus possibly expanding PipX roles beyond NtcA-dependency. Further exploration of these roles has revealed a functional interaction of PipX with PipY, a pyridoxal-phosphate (PLP) protein involved in PLP homeostasis whose mutations in the human ortholog cause epilepsy. Knowledge of cellular levels of the different components of this PII-PipX regulatory network and of KD values for some of the complexes provides the basic background for gross modeling of the system at high and low nitrogen abundance. The cyanobacterial network can guide searches for analogous components in other organisms, particularly of PipX functional analogs.