Sensory Mechanisms in Bacteria: Molecular Aspects of Signal Recognition | Book
Caister Academic Press
and Ray Dixon2
1 Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, Texas 75083-0688, USA
2 Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK
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September 2010Buy book
GB £159 or US $319
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Bacteria have evolved extraordinary abilities to regulate aspects of their behaviour (such as gene expression) in response to signals in the intracellular and extracellular environment. Key to this are the diverse macromolecules (proteins or RNA) that sense change through direct interactions with chemical or physical stimuli. In recent years there have been tremendous advances in our understanding of the structure and function of these signal receptors, and of how interaction with the signal triggers changes in their activity and downstream events. For some systems this understanding extends to the atomic level.
In this unique book, an international team of experts reviews a selection of important model systems, providing a timely snapshot of the current state of research in the field. The book opens with an introductory chapter that reviews the diversity of signal recognition mechanisms, illustrating the breadth of the field. Subsequent chapters include descriptions of the sensing of ligands (α-ketoglutarate, adenylate energy charge, glutamine and xenobiotic compounds), chemoreceptors, iron-sulfur cluster-based sensors, metal-dependent and metal-responsive sensors, thiol-based sensors, and PDZ domains as sensors of other proteins. This book provides essential reading for everyone with an interest in sensory mechanisms, regulatory networks and responses to environmental stress in bacteria.
"an excellent volume, put together thoughtfully to give good coverage of a complex and fascinating subject, which should grace any microbiology library" from Microbiology Today
Natural history of sensor domains in bacterial signaling systems
L. Aravind, Lakshminarayan M. Iyer and Vivek Anantharaman
Organisms sense stimuli at the molecular level using a relatively small set of protein domains. Computational analysis of protein sequences along with directed experimental studies have played a major role in the characterization of these protein domains. These sensor domains directly or indirectly detect a vast array of sensory inputs such as solutes, gases, redox potential and light. Here, we systematically survey the types of sensor domains found in bacterial signaling proteins. We summarize the key aspects of their structure that are central to their functions and their associations with other signaling domains. Despite the advances several of these domains remain poorly understood in terms of their structure, ligands and functional significance. We accordingly try to highlight the significance of some of the under-appreciated sensor domains. Genomic analysis reveals that the architectural complexity of sensory domains increases with the number of sensor proteins in a genome, with a gradual plateau towards a point where newer combinations of domains do not provide major selective advantage. Syntactical analysis of domain architectures shows several discernable patterns that have functional relevance, especially in terms of the constraints introduced by signal transmission domains such as HAMP and S-helix modules. Across bacteria, the number of signaling proteins shows a positive correlation with respect to proteome size. However, there is a clear distinction in the trends between bacteria that react directly and rapidly to a large number of small molecule signals vis-à-vis those that possess distinct signaling systems related to developmental complexity. Analysis of scaling trends for individual sensor domains shows that lifestyle strategies play a major role in the selection of the type and number of these domains in an organism. From an evolutionary viewpoint, the vast majority of sensory domains appear to have their origins in the bacteria and have been widely transferred to other superkingdoms of life. In particular most major eukaryotic sensor domains appear to have their antecedents in bacteria.
Sensing ligands by periplasmic sensing histidine kinases with sensory PAS domains
H. Kneuper, P. Scheu, M. Etzkorn, M. Sevvana, P. Dünnwald, S. Becker, M. Baldus, C. Griesinger, and G. Unden
Structural analysis demonstrated that the sensing domains from extracellular sensing histidine kinases revealed frequently the presence of a PAS domains with an untypical fold (PDC or periplasmic PASP fold). The PDC/PASP-fold differs from the common PAS-fold of cytoplasmic PAS domains. The structures of the PDC domains of the PDC domains of the tri- and dicarboxylate sensors CitA, DcuS and DctB, the antimicrobial peptide/divalent cation sensor PhoQ, and the quorum sensor LuxQ provide insights into mechanisms of signal perception. Different modes of signal processing were suggested despite similar folds of the PDC domains. The structures of the PDC/PASP domain of CitA in the citrate-bound and citrate-free form show contraction of the domain after citrate binding and suggest a vectorial movement of transmembrane helix TM2 to the periplasmic side, and signal transduction across the membrane by a piston-type movement. Structural information on signal transfer from the membrane to the kinase was elaborated for a membrane-embedded construct of DcuS. DcuS contains a cytoplasmic PAS (PASC) domain with a typical PAS-fold as a linker between TM2 and the kinase domain. PASC shows high intrinsic plasticity. It is suggested that the signal induced movement of TM2 is perceived by PASC resulting in a partial resolution of PASC dimerization and signal transmission to the kinase domains. Further structural and biochemical information for this class of histidine kinases will hopefully increase our insight into the processes of signal perception and signal transduction by transmembrane sensor kinases.
Sensation of α-ketoglutarate, adenylate energy charge, and glutamine, and signal integration by the nitrogen assimilation control system of Escherichia coli
Alexander J. Ninfa and Peng Jiang
In Escherichia coli and related bacteria, nitrogen assimilation is coordinated with carbon assimilation and cellular energy status to provide for balanced metabolism and optimal growth under a variety of conditions. Part of this regulation is accomplished by a signal transduction system that includes two bicyclic cascades of covalent modification, controlling the activity of glutamine synthetase and the transcription of nitrogen-regulated genes, respectively. Here, we review our current state of understanding of these bicyclic cascade systems, with an emphasis on the mechanisms of sensation and signal integration. We also address systems level questions relevant to sensation, focusing on how the relative levels of the proteins constituting the signal transduction system affects the sensitivity to signals, how zero-order and multi-step ultrasensitivity affect the sensitivity to signals, and how downstream targets of the signaling systems may influence sensation of stimuli and signal transduction.
Sensing xenobiotic compounds: Lessons from bacteria that face pollutants in the environment
Víctor de Lorenzo, Rafael Silva-Rocha, Guillermo Carbajosa, Teca C. Galvão and Ildefonso Cases
Bacteria that inhabit sites with a history of pollution by chemical waste possess an astonishing ability of evolving new pathways for catabolism of otherwise recalcitrant and/or xenobiotic compounds. The emergence of such pathways is often accompanied by the appearance of transcriptional regulatory circuits that adjust the levels of biodegradative activity to the available concentrations of cognate substrate(s). In addition, such circuits compute substrate levels along with their toxicity. In this way, the corresponding sensor systems implement a distribution of cell resources between functions for enduring stress and for metabolization of the target chemical. More than 90 transcription factors belonging to 10 different protein families are known to this day to regulate expression of biodegradative genes and operons for catabolism of persistent and xenobiotic molecules. In other cases, a number of regulatory proteins control expression of extrusion pumps for toxic chemicals or an excess of metabolic intermediates thereof. Experimental evolution studies made with a diversity of prokaryotic regulators that respond to such compounds (XylR, XylS, NahR, TetR and others) have revealed some mechanisms by which non-natural small molecules may become inducers upon binding these proteins. In some studied cases, such factors regress into functionally multi-potent, promiscuous forms (i.e., stem protein types) as a first step towards the divergence of novel effector specificities. Such an evolutionary frame provides a rationale for producing regulators á la carte responsive to synthetic chemical species.
Bacterial chemoreceptors as membrane-spanning allosteric enzymes
Michael D. Manson
This review approaches bacterial chemoreceptors from the standpoint that they are allosteric enzymes. What is conventionally thought of as the receptor itself, the transmembrane homodimer, is the regulatory subunit. The allosteric ligand binds to an extracellular (or periplasmic, in the case of Gram-negative bacteria) domain of a homodimeric protein, usually at the interface of the two subunits. This binding triggers a transmembrane signal that is propagated to the distal cytoplasmic tip of the dimer to modulate the activity of the catalytic subunit, a histidine protein kinase (HPK) known as CheA. The ligand can be either a negative or positive regulator of kinase activity. A schematic view of the overall structure is shown in Figure 1. It is also becoming increasingly clear that higher-order allosteric interactions among larger groups of receptors are essential for achieving the high sensitivity and sophisticated signal integration characteristic of bacterial chemotaxis (Hazelbauer et al., 2008). The best-studied receptors are those of the enteric bacteria Escherichia coli and Salmonella enterica. For that reason, and because the author works with E. coli, this review will focus on those two species. However, important differences in chemoreceptor structure and function in other bacteria will be noted from time to time. A nice summary of the diversity - and the underlying unity - that exists across the bacterial domain can be found in Alexander and Zhulin (2007). Macnab (1996) and Stock and Surette (1996) provide comprehensive reviews of the older work on motility and chemotaxis in E. coli and S. enterica, and the roles of chemoreceptors in transmembrane signaling have also been reviewed in detail (Falke and Hazelbauer, 2001; Miller and Falke, 2004).
Iron-sulfur cluster-based sensors
Jeffrey Green, Jason C. Crack, Adrian J. Jervis, David P. Dibden, Laura J. Smith, Andrew J. Thomson and Nick E. Le Brun
Iron-sulfur clusters are an ancient and important class of co-factor inherited from early anaerobic life forms. The most commonly encountered type of iron-sulfur cluster have between two and four iron atoms coordinated to the polypeptide backbone and bridged by inorganic sulfide. They are highly stable in anaerobic solution, even self-assemblying in vitro if an appropriate scaffold is provided, but inherently unstable in aerobic solutions. The in vivo assembly of iron-sulfur clusters is closely regulated and requires dedicated enzymes encoded by the suf, isc or nif operons, with the majority of living organisms having retained iron-sulfur clusters as catalysts, electron transfer agents, structural elements, or, more intriguingly, as sensors. In this chapter, we briefly summarise iron-sulfur cluster biogenesis before discussing specific examples of iron-sulfur cluster sensory proteins in which the status of the iron-sulfur cluster represents a key decision point within a regulatory network in response to important environmental cues.
Metal-dependent and metal-responsive regulatory systems
John D. Helmann
Metal ions play key roles in bacterial sensory systems as both cofactor and signal. Here, we distinguish between those sensors that require a metal ion for signal perception (metal-dependent sensors) and those for which the metal itself is the signal (metalloregulatory proteins). Metal-dependent sensors most commonly use either iron or zinc as cofactor. Iron-dependent, metal-dependent sensors figure prominently in pathways that orchestrate responses to reactive oxygen/nitrogen species. Examples include PerR, which senses hydrogen peroxide by metal-catalyzed protein oxidation, and NorR, which senses nitric oxide by nitrosylation of a non-heme iron atom. Zinc-dependent sensors often use reactive cysteine thiolates to sense reactive oxygen species (as in RsrA and Hsp33) or alkylating agents (Ada). Metalloregulatory proteins sense metal ions by their reversible interaction with specific sensory sites and, in response, coordinate appropriate transcriptional (and less commonly translational) responses. Nutrient metal ions commonly act as co-factors for transcriptional repressors and thereby repress uptake pathways. Conversely, toxic levels of metal ions will trigger derepression or activation of efflux or sequestration mechanisms. Here, we review the major families of metalloregulatory proteins and the general bioinorganic principles governing their function in the cytosol.
Thiol-based sensory factors
Haike Antelmann and Peter Zuber
Bacteria regularly encounter Reactive Oxygen, Nitrogen and Electrophilic Species (ROS, RNS, RES) that are generated inside the cells by incomplete reduction of molecular oxygen, imbalanced metabolic processes or applied externally by toxic or antimicrobial compounds. The response to such reactive agents is mediated by redox-sensitive transcription factors that exploit the unique chemistry of cysteine thiol groups. Redox-sensitive regulatory proteins bear cysteine residues that can undergo post-translational modification, leading to either activation or inactivation of the transcription factors. This in turn results in responses that are aimed to detoxify the reactive species or alleviate the damage they cause. Different thiol-modifications are implicated in redox-sensing depending on the number of redox-active Cys residues and their reactivity, the oxidant to which they react, and the prevailing in vitro or in vivo conditions. Redox-sensitive proteins with more than one reactive Cys residue undergo in most cases reversible inter- and/or intramolecular disulfide linkages, which serve as sensing mechanisms for OxyR, the 2-Cys OhrR family, MexR, OspR, Spx, CprK and CrtJ. In contrast to these classical thiol-disulfide-switches, transcription factors with one redox-active Cys residue are reversibly regulated via initial sulphenic acid formation, S-thiolation with low molecular weight (LMW) thiols and sulfenamide formation with the backbone amide as shown for OxyR, the 1-Cys OhrR ortholog, MgrA and SarZ. However, the thiol group of the 1-Cys OhrR protein can also be irreversibly modified by overoxidation to sulfinic and sulfonic acids in response to strong oxidants. RES such as quinones were shown to modify the YodB repressor irreversibly by thiol-(S)-alkylation. In addition to redox-sensing transcription factors, LMW thiols and the thioredoxin/thioredoxin reductase system maintain the thiol-redox-balance of the cell upon exposure to reactive species. Here we review (1) enzymatic redox control mechanisms by thiol-disulfide reductases and (2) the current knowledge of bacterial redox-sensitive transcription factors that function without metal cofactors, including OxyR, OhrR, MexR, OspR, MgrA, SarZ, YodB, Spx, CprK and PspR/CrtJ. Each of these transcription factors senses unique signals including ROS, RNS, RES, antibiotic and haloorganic compounds, or the cellular oxygen level and light that are transduced via diverse redox-sensing mechanisms involving different reversible and irreversible thiol-modifications.
PDZ domains as sensors of other proteins
Rebecca Kirk and Tim Clausen
Proteins containing PDZ domains have been shown to mediate a wide range of protein-protein interactions and to function as molecular scaffolds in the assembly of multi-protein complexes. The most studied typical function of PDZ domains is to recognize and bind short specific sequences at the C-terminal tails of their interacting partners; however other PDZ-mediated interactions including the recognition of internal motifs have been reported. PDZ domains are frequently combined with catalytic domains like, for example, protease, kinase and phosphatase domains. In this case, the PDZ domains do not simply function as molecular glue bringing entities of signaling cascades in contact with each other, but rather exert important regulatory functions by controlling the activity of their co-working partner domain. For one class of PDZ-enzymes, the HtrA proteases, the inter-domain communication has been studied in molecular detail providing the first insight into how PDZ domains control enzyme function and sense different external stimuli. HtrA proteins function to monitor protein homeostasis in the cell. In prokaryotes this family of proteins underpins processes required for tolerance against various folding stresses and pathogenicity. Human HtrA proteins are involved in mammalian stress response pathways and in the prevention of the onset of protein misfolding diseases: including arthritis, Parkinson's and Alzheimer's disease. Recent biochemical and structural data indicate that the PDZ domains of HtrA proteins could act as sensors of folding stress, autoproteolysis, misfolded proteins, cleavage products and of specific interaction partners. As detailed in this review, interactions undergone with the PDZ domain are the starting point of an intramolecular signaling mechanism that ultimately modulates the activity of the attached catalytic domain. In this review we will focus on the function of PDZ domains as sensors for various peptide and protein signals. We will introduce PDZ domains and describe PDZ-enzymes. Of these the best understood is the family of HtrA proteases, whose structures, functions, signals and downstream cascades will be described. Finally we will discuss the recent findings illustrating how PDZ domains couple the sensing of various stimuli with the adjustment of protease function.
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(EAN: 9781904455691 Subjects: [bacteriology] [microbiology] [molecular microbiology] [bacterial regulation] )