A connector of two-component regulatory systems promotes signal amplification and persistence of expression

Abstract

Organisms rely on a variety of regulatory architectures to control gene transcription. Whereas the functional characteristics of particular architectures are well understood, the properties of newly discovered regulatory designs cannot be easily predicted. One emerging design depends on small proteins that connect twocomponent regulatory systems, which constitute the dominant form of bacterial signal transduction. These connectors enable one system to respond to the signal perceived by a different system. To understand the functional properties of such connector-mediated architectures, we investigated the pathway controlled by the PhoP-dependent connector protein PmrD of Salmonella enterica and contrasted it to the circuit in which genes are regulated directly by the transcription factor PhoP. The PmrD-mediated pathway displayed both signal amplification and persistence of expression when compared with the direct pathway. Mathematical modeling of the two pathways allowed us to identify critical factors responsible for signal amplification. mathematical modeling ͉ Salmonella ͉ signal transduction ͉ transcriptional regulatory circuit ͉ two-component system

The BLUF-EAL protein YcgF acts as a direct anti-repressor in a blue-light response of Escherichia coli

“…They provide additional signal input not perceived by the sensory input domains of the sensor kinases, and thereby connect two-component systems to other regulatory pathways. Connectors can affect phosphorylation, phosphotransfer, and dephosphorylation reactions within simple two-component or more complex phosphorelay systems or they may sequester a component of such a pathway (Kato and Groisman 2004;Bougdour et al 2006Bougdour et al , 2008Eguchi et al 2007;Kato et al 2007). How YmgB and probably also YmgA and YcgZ affect the activity of the Rcs phosphorelay will have to be investigated in future genetic and biochemical studies.…”

Positive feedback in cellular control systems

“…(99,100) Combinations of these elements often display qualities that the separate components do not possess, thus providing the foundation for the diversity of cellular control processes. Understanding of the properties of PFLs and their interactions with other regulatory elements will help to improve our ability to predict the behavior of regulatory circuits in living cells and to construct biomolecular systems with desired characteristics.…”

Resistance to Colistin in Acinetobacter baumannii Associated with Mutations in the PmrAB Two-Component System

“…A small adapter protein, PmrD, serves as an interface between the two-component systems by stabilizing the activated form of PmrA in S. enterica (19), but other mechanisms of coordinated regulation are described for other species (52). Mutations causing constitutive activation of PmrA and PmrB are associated with colistin resistance (31,33).…”