Comparative analysis of prototype two‐component systems with either bifunctional or monofunctional sensors: differences in molecular structure and physiological function

Abstract

SummarySignal transduction by a traditional two-component system involves a sensor protein that recognizes a physiological signal, autophosphorylates and transfers its phosphate, and a response regulator protein that receives the phosphate, alters its affinity toward specific target proteins or DNA sequences and causes change in metabolic activity or gene expression. In some cases the sensor protein, when unphosphorylated, has a positive effect upon the rate of dephosphorylation of the regulator protein (bifunctional sensor), whereas in other cases it has no such effect (monofunctional sensor). In this work we identify structural and functional differences between these two designs. In the first part of the paper we use sequence data for two-component systems from several organisms and homology modelling techniques to determine structural features for response regulators and for sensors. Our results indicate that each type of reference sensor (bifunctional and monofunctional) has a distinctive structural feature, which we use to make predictions regarding the functionality of other sensors. In the second part of the paper we use mathematical models to analyse and compare the physiological function of systems that differ in the type of sensor and are otherwise equivalent. Our results show that a bifunctional sensor is better than a monofunctional sensor both at amplifying changes in the phosphorylation level of the regulator caused by signals from the sensor and at attenuating changes caused by signals from small phosphodonors. Crosstalk to or from other two-component systems is better suppressed if the transmitting sensor is monofunctional, which is the more appropriate design when such cross-talk represents pathological noise. Crosstalk to or from other two-component systems is better amplified if the transmitting sensor is bifunctional, which is the more appropriate design when such cross-talk represents a physiological signal. These results provide a functional rationale for the selection of each design that is consistent with available experimental evidence for several two-component systems.

A Sensor of the Two-Component System CpxA Affects Expression of the Type III Secretion System through Posttranscriptional Processing of InvE

“…CpxA has little effect on virF expression; however, CpxR is essential for the transcription of virF (28). In cpxA mutants, several genes under Cpx regulation have been shown to be transcribed at levels similar to those in the wildtype strain (3,8). These phenomena are explained by the phosphatase activity of CpxA.…”

Cyanobacterial Two-Component Proteins: Structure,Diversity, Distribution, andEvolution

“…Compared to most other bacteria, the large number of GAF domains correlates and underlines the role of light in the regulation of gene expression and metabolic activities for photosynthetic organisms (40). None of the seven marine unicellular non-N 2 -fixing strains have any HKIIϩGAF, and only four of them have HKIIϩ(PAS) [1][2][3] …”

“…strain 9902, or P. marinus SS120 and MIT9313. T. erythraeum (Chk78) has a HKIIϩ(PAS) [1][2][3] that is orthologous to those of Anabaena sp. strain PCC 7120 and N. punctiforme paralogues of Chk7.…”

“…They can be found in most terrestrial, freshwater, and marine habitats (28). Like most bacteria, cyanobacteria use two-component regulatory systems proteins to regulate cell behavior and gene expression in response to changes in the external environment (3,24,54,56,80,132,136,140). Twocomponent systems typically consist of two types of proteins, histidine kinases (HK) and response regulators (RR), which may sometimes be carried by a single polypeptide to form the hybrid kinases (HY).…”

Signal amplification in biological and electrical engineering systems

“…The complexity of cellular signalling depends on the complexity of living organisms and on the cell type. In prokaryotes, for example, simple one-and twocomponent systems link external signals with cellular responses [1,2]. In plant and animal cells, signalling networks can be highly complex, some networks comprising of 60 or more proteins [3].…”