Abstract
PipX is a unique cyanobacterial protein identified by its ability to bind to PII and NtcA, two key regulators involved in the integration of signals of the nitrogen/carbon and energy status, with a tremendous impact on nitrogen assimilation and gene expression in cyanobacteria. PipX provides a mechanistic link between PII, the most widely distributed signaling protein, and NtcA, a global transcriptional regulator of cyanobacteria. PII, required for cell survival unless PipX is inactivated or down-regulated, functions by protein–protein interactions with transcriptional regulators, transporters, and enzymes. In addition, PipX appears to be involved in a wider signaling network, supported by the following observations: (i) PII–PipX complexes interact with PlmA, an as yet poorly characterized transcriptional regulator also restricted to cyanobacteria; (ii) the pipX gene is functionally connected with pipY, a gene encoding a universally conserved pyridoxal phosphate binding protein (PLPBP) involved in vitamin B6 and amino acid homeostasis, whose loss-of-function mutations cause B6-dependent epilepsy in humans, and (iii) pipX is part of a relatively robust, six-node synteny network that includes pipY and four additional genes that might also be functionally connected with pipX. In this overview, we propose that the study of the protein–protein interaction and synteny networks involving PipX would contribute to understanding the peculiarities and idiosyncrasy of signaling pathways that are conserved in cyanobacteria.
Highlights
Cyanobacteria, phototrophic organisms that perform oxygenic photosynthesis, constitute an ecologically important phylum that is responsible for the evolution of the oxygenic atmosphere, and are the main contributors to marine primary production [1]
Cyanobacteria have developed sophisticated systems to maintain the homeostasis of carbon/nitrogen, the two most abundant nutrient elements in all living forms; understanding the regulatory mechanisms affecting their metabolic balance is of paramount importance from the biotechnological as well as the environmental points of view
Yeast three-hybrid searches with PipX–PII as bait resulted in the identification of the cyanobacterial transcriptional regulator PlmA as an interacting protein [29], while co-expression and synteny approaches functionally connected PipX with PipY, a conserved pyridoxal phosphate-binding protein involved in amino/keto acid and pyridoxal phosphate (PLP) homeostasis [30,31,32]
Summary
Cyanobacteria, phototrophic organisms that perform oxygenic photosynthesis, constitute an ecologically important phylum that is responsible for the evolution of the oxygenic atmosphere, and are the main contributors to marine primary production [1] Their photosynthetic lifestyle and ease of cultivation make them ideal production systems for a number of high-value compounds, including biofuels [2]. PipX was found as prey in yeast two-hybrid searches with NtcA, the global transcriptional regulator involved in nitrogen assimilation in cyanobacteria [14,15]. Yeast three-hybrid searches with PipX–PII as bait resulted in the identification of the cyanobacterial transcriptional regulator PlmA as an interacting protein [29], while co-expression and synteny approaches functionally connected PipX with PipY, a conserved pyridoxal phosphate-binding protein involved in amino/keto acid and pyridoxal phosphate (PLP) homeostasis [30,31,32]
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