A catalogue of signal molecules that interact with sensor kinases, chemoreceptors and transcriptional regulators

FEMS Microbiology Reviews, Год журнала: 2021, Номер 46(1)

Опубликована: Авг. 10, 2021

Bacteria have evolved many different signal transduction systems that sense signals and generate a variety of responses. Generally, most abundant are transcriptional regulators, sensor histidine kinases chemoreceptors. Typically, these recognize their molecules with dedicated ligand-binding domains (LBDs), which, in turn, molecular stimulus modulates the activity output module. There an enormous number LBDs similarly diverse set signals. To give global perspective interact chemoreceptors, we manually retrieved information on protein-ligand interaction from about 1,200 publications 3D structures. The resulting 811 proteins were classified according to Pfam family into 127 groups. These data permit delineation profiles individual LBD families as well distinguishing between promiscuous manner those possess well-defined ligand range. A major bottleneck field is fact input signaling unknown. repertoire reported here will help scientific community design experimental strategies identify for uncharacterised proteins.

Язык: Английский

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Bacterial second messenger c-di-GMP: Emerging functions in stress resistance

Microbiological Research, Год журнала: 2023, Номер 268, С. 127302 - 127302

Опубликована: Янв. 11, 2023

Язык: Английский

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Origin and functional diversification of PAS domain, a ubiquitous intracellular sensor

Science Advances, Год журнала: 2023, Номер 9(35)

Опубликована: Авг. 30, 2023

Signal perception is a key function in regulating biological activities and adapting to changing environments. Per-Arnt-Sim (PAS) domains are ubiquitous sensors found diverse receptors bacteria, archaea, eukaryotes, but their origins, distribution across the tree of life, extent functional diversity not fully characterized. Here, we show that using sequence conservation structural information, it possible propose specific potential functions for large portion nearly 3 million PAS domains. Our analysis suggests originated bacteria were horizontally transferred archaea eukaryotes. We reveal gas sensing via heme cofactor evolved independently several lineages, whereas redox light flavin adenine dinucleotide mononucleotide cofactors have same origin. The close relatedness human those provides an opportunity drug design by exploring natural ligands bacterial homologs.

Язык: Английский

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Phospho-relay feedback loops control egress vs. intracellular development in Toxoplasma gondii

Cell Reports, Год журнала: 2025, Номер 44(2), С. 115260 - 115260

Опубликована: Фев. 1, 2025

Highlights•Protein kinase Ac1 inhibits egress in Toxoplasma by suppressing calcium signaling•Adenylate cyclase ACα3 and phosphodiesterase 2 control cAMP to regulate PKAc1•PKAc1 phosphorylates PDE2 cleave form a negative feedback loop•PKAc1 acts on targets between cGMP release prevent egressSummaryThe intracellular parasite gondii alternates motile invasive quiescent replicative form, yet how these transitions are regulated is unknown. A positive loop involving protein G (PKG) calcium-dependent PKs (CDPKs) controls motility, invasion, gondii, while PKA isoform c1 (PKAc1) counteracts this pathway. Shortly after PKAc1 activated cyclic AMP (cAMP) produced adenylate cyclases, leading the suppression of PKG/CDPK further activates 2, which selectively consumes cAMP, thus forming loop, causing transient activation PKAc1. Perturbation GMP (cGMP) vs. demonstrates that guanylate release. The combined PKG/CDPKs inhibition PKAc1, controlled ensures responsive environmental signals needed activate motility also ensuring periods long-term stable growth.Graphical abstract

Язык: Английский

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All DACs in a Row: Domain Architectures of Bacterial and Archaeal Diadenylate Cyclases

Journal of Bacteriology, Год журнала: 2023, Номер 205(4)

Опубликована: Апрель 6, 2023

Cyclic dimeric AMP (c-di-AMP) is a widespread second messenger that controls such key functions as osmotic homeostasis, peptidoglycan biosynthesis, and response to various stresses. C-di-AMP synthesized by diadenylate cyclases contain the DAC (DisA_N) domain, which was originally characterized N-terminal domain in DNA integrity scanning protein DisA. In other experimentally studied cyclases, typically located at C termini its enzymatic activity controlled one or more domains. As bacterial signal transduction proteins, these modules appear sense environmental intracellular signals through ligand binding and/or protein-protein interactions. Studies of archaeal also revealed numerous sequences with uncharacterized regions. This work provides comprehensive review domains including description five previously undefined three PK_C-related DacZ_N superfamily. These data are used classify into 22 families, based on their conserved architectures phylogeny Although nature regulatory remains obscure, association certain dac genes anti-phage defense CBASS systems phage-resistance suggests c-di-AMP might be involved signaling phage infection.

Язык: Английский

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Blue-light irradiation induced partial nitrification

Water Research, Год журнала: 2024, Номер 254, С. 121381 - 121381

Опубликована: Фев. 27, 2024

Язык: Английский

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How c-di-GMP controls progression through the Streptomyces life cycle

Current Opinion in Microbiology, Год журнала: 2024, Номер 80, С. 102516 - 102516

Опубликована: Июль 26, 2024

Members of the antibiotic-producing bacterial genus Streptomyces undergo a complex developmental life cycle that culminates in production spores. Central to control this cell differentiation process is signaling through second messenger 3′, 5′-cyclic diguanylic acid (c-di-GMP). So far, three proteins are directly controlled by c-di-GMP have been functionally and structurally characterized: key regulators BldD σWhiG, glycogen-degrading enzyme GlgX. signals respectively, two most dramatic transitions cycle, formation reproductive aerial hyphae their into spore chains. Later development, activates GlgX-mediated degradation glycogen, releasing stored carbon for maturation.

Язык: Английский

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Bioinformatic and genomic analyses on FlrB–FlrC-type TCS orthologs involved in flagellar synthesis of monotrichous Gram-negative bacteria

Journal of Proteins and Proteomics, Год журнала: 2025, Номер unknown

Опубликована: Март 18, 2025

Язык: Английский

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Structural and functional diversity of sensor domains in bacterial transmembrane receptors

Trends in Microbiology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Evidence of Bidirectional Transmembrane Signaling by the Sensor Histidine Kinase GacS from Pseudomonas aeruginosa

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108521 - 108521

Опубликована: Апрель 1, 2025

Membrane-embedded signaling Histidine Kinases (SKs) from two-component and phosphorelay signal transduction systems play central roles in the gene regulation of bacteria, fungi, plants. The SK GacS is a global regulator expression human pathogen Pseudomonas aeruginosa. interactions between another SK, RetS, are model for studying non-canonical crosstalk multikinase networks. During planktonic growth, RetS inhibits to upregulate virulence factors associated with acute P. aeruginosa infections repress genes linked chronic infection. Conversely, activation promotes biofilm formation infection but suppresses required during Using combination hydrogen-deuterium exchange mass spectrometry (HDX-MS) mutational analysis conjunction functional assays, we show that binding an extracellular ligand through two mechanisms: (1) by increasing autokinase activity (2) decreasing affinity RetS. Intriguingly, intracellular histidine kinase domain also triggered conformational changes sensory GacS. This allosteric effect was confirmed biochemical assay, showing increases chimeric CitAGacS receptor citrate almost tenfold. finding establishes first precedent inside-out cross-membrane systems. Taken together, our data consistent wherein primes sensing growth. Binding unknown at onset causes dissociation RetS-GacS complex lock ON conformation.

Язык: Английский

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