Structural basis for CaVα2δ-gabapentin binding DOI Creative Commons
Abhisek Mondal, Zhou Chen, Daniel L. Minor

et al.

Biophysical Journal, Journal Year: 2024, Volume and Issue: 123(3), P. 443a - 443a

Published: Feb. 1, 2024

Language: Английский

Pseudomonas syringae pv. tomato infection of tomato plants is mediated by GABA and l‐Pro chemoperception DOI Creative Commons
Saray Santamaría‐Hernando,

Álvaro López‐Maroto,

Clara Galvez‐Roldán

et al.

Molecular Plant Pathology, Journal Year: 2022, Volume and Issue: 23(10), P. 1433 - 1445

Published: June 10, 2022

Foliar bacterial pathogens have to penetrate the plant tissue and access interior of apoplast in order initiate pathogenic phase. The entry process is driven by chemotaxis towards plant-derived compounds locate openings. However, information on signals recognized chemoreceptors scarce. Here, we show that perception GABA l-Pro, two abundant components tomato apoplast, through PsPto-PscC chemoreceptor drives Pseudomonas syringae pv. into apoplast. recognition both caused chemoattraction amino acids participated regulation catabolism. Mutation a reduced chemotactic response these which turn impaired virulence plants. Interestingly, l-Pro levels significantly increase plants upon pathogen infection are involved defence response. This an example illustrating how bacteria respond produced during interaction as cues ensure efficient infection.

Language: Английский

Citations

27

Amine-recognizing domain in diverse receptors from bacteria and archaea evolved from the universal amino acid sensor DOI Creative Commons
Jean Paul Cerna‐Vargas, Vadim M. Gumerov, Tino Krell

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(42)

Published: Oct. 11, 2023

Bacteria possess various receptors that sense different signals and transmit information to enable an optimal adaptation the environment. A major limitation in microbiology is lack of on signal molecules activate receptors. Signals recognized by sensor domains are poorly reflected overall sequence identity, therefore, identification from amino acid alone presents a challenge. Biogenic amines great physiological importance for microorganisms humans. They serve as substrates aerobic anaerobic growth play role neurotransmitters osmoprotectants. Here, we report motif specific amine-sensing belong Cache superfamily most abundant extracellular sensors prokaryotes. We identified approximately 13,000 histidine kinases, chemoreceptors, involved second messenger homeostasis Ser/Thr phosphatases 8,000 bacterial archaeal species contain amine-recognizing motif. The screening compound libraries microcalorimetric titrations selected confirmed their ability specifically bind biogenic amines. Mutants amine-binding or single mismatch binding had either no largely reduced affinity demonstrate domain originated universal acid–sensing domain, thus providing insight into receptor evolution. Our approach enables precise “wet”-lab experiments define function regulatory systems therefore holds strong promise stimulating numerous

Language: Английский

Citations

15

Framework for exploring the sensory repertoire of the human gut microbiota DOI Creative Commons

Patricia A. Ross,

Wenhao Xu, Ekaterina Jalomo-Khayrova

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(6)

Published: May 17, 2024

ABSTRACT Bacteria sense changes in their environment and transduce signals to adjust cellular functions accordingly. For this purpose, bacteria employ various sensors feeding into multiple signal transduction pathways. Signal recognition by bacterial is studied mainly a few model organisms, but advances genome sequencing analysis offer new ways of exploring the sensory repertoire many understudied organisms. The human gut natural target line study: it nutrient-rich dynamic home thousands species whose activities impact health. Many commensals are also poorly compared organisms known through sequences. To begin respond to, we have designed framework that enables identification domains, prediction they recognize, experimental verification these predictions. We validate framework’s functionality systematically identifying amino acid selected genomes metagenomes, characterizing binding properties, demonstrating potential. IMPORTANCE central process governing how environment. complex with living fluctuating streams nutrients. One inhabitant, Escherichia coli , organism for studying transduction. However, E. not representative most microbes, signaling pathways other comprising microbiota remain understood. This work provides foundation explore recognized

Language: Английский

Citations

5

Three unrelated chemoreceptors provide Pectobacterium atrosepticum with a broad‐spectrum amino acid sensing capability DOI Creative Commons
Félix Velando, Miguel A. Matilla, Igor B. Zhulin

et al.

Microbial Biotechnology, Journal Year: 2023, Volume and Issue: 16(7), P. 1548 - 1560

Published: March 25, 2023

Abstract Amino acids are important nutrients and also serve as signals for diverse signal transduction pathways. Bacteria use chemoreceptors to recognize amino acid attractants navigate their gradients. In Escherichia coli two likely paralogous Tsr Tar detect 9 acids, whereas in Pseudomonas aeruginosa the PctA, PctB PctC 18 acids. Here, we show that phytobacterium Pectobacterium atrosepticum uses three non‐homologous PacA, PacB PacC 19 proteinogenic several non‐proteinogenic recognizes well 8 has a ligand preference branched chain L‐leucine, L‐valine L‐isoleucine. PacA detects L‐proline next quaternary amines. The third chemoreceptor, PacC, is an ortholog of E. only one 36 P. encoded cluster chemosensory pathway genes. Surprisingly, contrast Tsr, which primarily senses serine, aspartate major chemoeffector but not serine. Our results demonstrate bacteria various strategies sense wide range it takes more than chemoreceptor achieve this goal.

Language: Английский

Citations

12

Structural and functional diversity of sensor domains in bacterial transmembrane receptors DOI
Miguel A. Matilla, J.A. Gavira, Elizabet Monteagudo‐Cascales

et al.

Trends in Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0

Systematic mapping of chemoreceptor specificities for Pseudomonas aeruginosa DOI Creative Commons
Wenhao Xu, Jean Paul Cerna‐Vargas, Ana Tajuelo

et al.

mBio, Journal Year: 2023, Volume and Issue: 14(5)

Published: Oct. 4, 2023

Chemotaxis of motile bacteria has multiple physiological functions. It enables to locate optimal ecological niches, mediates collective behaviors, and can play an important role in infection. These functions largely depend on ligand specificities chemoreceptors, the number identities chemoreceptors show high diversity between organisms. Similar is observed for spectra chemoeffectors, which include not only chemicals metabolic value but also bacterial, plant, animal signaling molecules. However, systematic identification chemoeffectors their mapping specific remains a challenge. Here, we combined several vivo vitro approaches establish screening strategy receptor ligands applied it identify new physiologically relevant opportunistic human pathogen P. aeruginosa. This be equally applicable map sensory domains from wide variety types bacteria.

Language: Английский

Citations

9

Recognition Mechanism of a Novel Gabapentinoid Drug, Mirogabalin, for Recombinant Human α2δ1, a Voltage-Gated Calcium Channel Subunit DOI Creative Commons
Daisuke Kozai, Nobutaka Numoto,

Kouki Nishikawa

et al.

Journal of Molecular Biology, Journal Year: 2023, Volume and Issue: 435(10), P. 168049 - 168049

Published: March 17, 2023

Mirogabalin is a novel gabapentinoid drug with hydrophobic bicyclo substituent on the γ-aminobutyric acid moiety that targets voltage-gated calcium channel subunit α2δ1. Here, to reveal mirogabalin recognition mechanisms of α2δ1, we present structures recombinant human α2δ1 and without analyzed by cryo-electron microscopy. These show binding previously reported site, which extracellular dCache_1 domain containing conserved amino motif. A slight conformational change occurs around residues positioned close group mirogabalin. Mutagenesis assays identified in interaction region, addition several motif carboxyl groups mirogabalin, are critical for binding. The A215L mutation introduced decrease pocket volume predictably suppressed promoted another ligand, L-Leu, smaller than Alterations region those α2δ2, α2δ3, α2δ4 isoforms, α2δ3 gabapentin-insensitive, results support importance interactions ligand recognition.

Language: Английский

Citations

7

Exploring the Metabolic Response of Pseudomonas putida to L-arginine DOI

Chiara Scribani-Rossi,

María Antonia Molina‐Henares, Manuel Espinosa‐Urgel

et al.

Advances in experimental medicine and biology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

2

The pH Robustness of Bacterial Sensing DOI Creative Commons
Elizabet Monteagudo‐Cascales, David Martín‐Mora, Wenhao Xu

et al.

mBio, Journal Year: 2022, Volume and Issue: 13(5)

Published: Sept. 26, 2022

Bacteria have evolved many different signal transduction systems to sense and respond changing environmental conditions. Signal integration is mainly achieved by recognition at extracytosolic ligand-binding domains (LBDs) of receptors. Hundreds LBDs been reported, our understanding their sensing properties growing. Receptors must function over a range pH values, but there little information available on the robustness as pH. Here, we used isothermal titration calorimetry determine dependence ligand nine that cover all major LBD superfamilies, periplasmic solute-binding proteins, cytosolic LBDs. We show recognize ligands very broad range, frequently stretching eight units. This wide contrasts with much narrower response analyzed. Many be dimeric bind ligands, analytical ultracentrifugation studies showed Tar chemoreceptor forms dimers entire tested. The dependences Pseudomonas aeruginosa motility chemotaxis were bell-shaped centered 7.0. Evidence for signaling in vivo was obtained Förster Resonance Energy Transfer (FRET) measurements pathway responses Escherichia coli. several strategies cope extreme pH, such chaperones protein refolding. intrinsic resistance appears another strategy permits bacteria survive under adverse IMPORTANCE Demonstration extracytoplasmic reveals previously undescribed evolutionary mechanism enables monitor changes includes maintenance state four-helixbundle (LBDs). construction biosensors rapidly growing field research, use progression COVID-19 pandemic has impressively demonstrated usefulness. represent an enormous reservoir binding modules can create novel biosensors. Among recognized are neurotransmitters, hormones, quorum-sensing signals. demonstration signals values will facilitate design highly variable conditions acidity alkalinity.

Language: Английский

Citations

11

Multiple detection of both attractants and repellents by the dCache‐chemoreceptor SO_1056 of Shewanella oneidensis DOI Creative Commons

Anne Boyeldieu,

Jean-Pierre Poli, Amine Ali Chaouche

et al.

FEBS Journal, Journal Year: 2022, Volume and Issue: 289(21), P. 6752 - 6766

Published: June 7, 2022

Chemoreceptors are usually transmembrane proteins dedicated to the detection of compound gradients or signals in surroundings a bacterium. After detection, they modulate activation CheA-CheY, core chemotactic pathway, allow cells move upwards downwards depending on whether signal is an attractant repellent, respectively. Environmental bacteria such as Shewanella oneidensis harbour dozens chemoreceptors MCPs (methyl-accepting chemotaxis proteins). A recent study revealed that MCP SO_1056 S. binds chromate. Here, we show this also detects additional (l-malate) and two repellents (nickel cobalt). The experiments were performed vivo by agarose-in-plug technique after overproducing vitro, when possible, submitting purified ligand-binding domain (LBD) thermal shift assay (TSA) coupled isothermal titration calorimetry (ITC). ITC assays KD 3.4 μm for l-malate 47.7 nickel. We conclude attractants unrelated composition. LBD belongs double Cache_1 family highly homologous PctA, chemoreceptor from Pseudomonas aeruginosa several amino acids. Therefore, LBDs same can bind diverse compounds, confirming experimental approaches required define accurate LBD-binding molecules signals.

Language: Английский

Citations

10