A5036730007- Nicotinic Acetylcholine Receptors Study
- Ion channel regulation and function
- Cancer Research and Treatments
- Amino Acid Enzymes and Metabolism
- RNA and protein synthesis mechanisms
- Molecular Sensors and Ion Detection
- RNA Research and Splicing
- Supramolecular Chemistry and Complexes
- Photoreceptor and optogenetics research
- Neuroscience and Neuropharmacology Research
- Antimicrobial Peptides and Activities
- Biochemical and Molecular Research
- Plant-based Medicinal Research
- Fungal and yeast genetics research
- Receptor Mechanisms and Signaling
- Peptidase Inhibition and Analysis
- Mass Spectrometry Techniques and Applications
- Anesthesia and Neurotoxicity Research
- Viral Infectious Diseases and Gene Expression in Insects
- Chemical Synthesis and Analysis
- Inorganic Fluorides and Related Compounds
- Optimization and Mathematical Programming
- Scheduling and Timetabling Solutions
- Advancements in Battery Materials
- Biopolymer Synthesis and Applications
Centre National de la Recherche Scientifique
2014-2025
Institut Pasteur
2015-2024
University of Sfax
2014-2023
Centre d'Immunologie et des Maladies Infectieuses
2020
Institut National de la Transfusion Sanguine
2019
Biologie Intégrée du Globule Rouge
2019
Université Paris Cité
2019
Inserm
2019
Centre National pour la Recherche Scientifique et Technique (CNRST)
2017
École Polytechnique
2014-2017
Significance Control of mRNA synthesis and decay is crucial for cells to adapt their environment proper development. The 5′ end eukaryotic mRNAs modified by a structure called cap that protects them from rapid uncontrolled decay. During decay, this removed specialized finely regulated multiprotein factory decapping complex. Our results support model in which the two major enzymes responsible (Dcp2) (Xrn1) are sequentially recruited same surface Pat1, scaffolding protein central decapping. As...
Allosteric modulation of pentameric ligand-gated ion channels (pLGICs) are critical for the action neurotransmitters and many psychoactive drugs. However, details their modulatory mechanisms remain unclear, especially beyond orthosteric neurotransmitter-binding sites. The recently reported prokaryotic symbiont Tevnia jerichonana channel (sTeLIC), a pH-gated homologue eukaryotic receptors in pLGIC family, is thought to be modulated by aromatic compounds via relatively uncharacterised site...
We previously designed a new family of artificial proteins named αRep based on subgroup thermostable helicoidal HEAT-like repeats. have now assembled large optimized library. In this library, the side chains at each variable position are not fully randomized but instead encoded by distribution codons natural frequency repeats family. The library construction is polymerization micro-genes and therefore results in with number improved process using "filtration" procedure to retain only coding...
Pentameric ligand-gated ion channels (pLGICs) mediate fast chemical signaling through global allosteric transitions. Despite the existence of several high-resolution structures pLGICs, their dynamical properties remain elusive. Using proton-gated channel GLIC, we engineered multiple fluorescent reporters, each incorporating a bimane and tryptophan/tyrosine, whose close distance causes fluorescence quenching. We show that proton application compaction extracellular subunit interface, coupled...
Ion channel modulation by general anesthetics is a vital pharmacological process with implications for receptor biophysics and drug development. Functional studies have implicated conserved sites of both potentiation inhibition in pentameric ligand-gated ion channels, but detailed structural mechanism these bimodal effects lacking. The prokaryotic model protein GLIC recapitulates anesthetic human it accessible to structure determination apparent open closed states. Here, we report ten X-ray...
The pentameric ligand-gated ion channel (pLGIC) from Gloeobacter violaceus (GLIC) has provided insightful structure–function views on the permeation process and allosteric regulation of pLGICs family. However, GLIC is activated by pH instead a neurotransmitter clear picture for gating transition driven protons still lacking. We used an electrostatics-based (finite difference Poisson–Boltzmann/Debye–Hückel) method to predict acidities all aspartic glutamic residues in GLIC, both its active...
GLIC receptor is a bacterial pentameric ligand-gated ion channel whose action inhibited by xenon. Xenon has been used in clinical practice as potent gaseous anaesthetic for decades, but the molecular mechanism of interactions with its integral membrane targets remains poorly understood. Here we characterize X-ray crystallography xenon-binding sites within both open and "locally-closed" (inactive) conformations GLIC. Major binding xenon, which differ between two conformations, were identified...
Pentameric ligand-gated ion channels (pLGICs) mediate fast chemical neurotransmission of nerve signalling in the central and peripheral nervous systems. GLIC is a bacterial homologue eukaryotic pLGIC, X-ray structure which has been determined three different conformations. thus widely used as model to study activation allosteric transition this family receptors. The recently solved high-resolution (2.4 Å resolution) active state revealed two bound acetate molecules extracellular domain...
Significance Pentameric ligand-gated ion channels (pLGICs) mediate fast signal transduction in animal nerve cells through neurotransmitters. Mutation of some these receptors the brain causes severe nervous system diseases. The high sequence diversity prokaryotic makes them unique model systems to understand evolutionary conservation gating and sensitivity allosteric modulators. We present 2.3 Å X-ray structure a pLGIC (sTeLIC) from gammaproteobacteria that is activated at alkaline pH. pH 8.0...
The Gloeobacter violaceus ligand-gated ion channel (GLIC) has been extensively studied by X-ray crystallography and other biophysical techniques. This provided key insights into the general gating mechanism of pentameric (pLGIC) signal transduction. However, GLIC is activated lowering pH location its putative proton activation site(s) still remain(s) unknown. To this end, every Asp, Glu, His residue was mutated individually or in combination investigated electrophysiology. In addition to...
Eukaryotic mRNA decay is a highly regulated process allowing cells to rapidly modulate protein production in response internal and environmental cues. Mature translatable eukaryotic mRNAs are protected from fast uncontrolled degradation the cytoplasm by two cis-acting stability determinants: methylguanosine (m7G) cap poly(A) tail at their 5′ 3′ extremities, respectively. The hydrolysis of m7G structure, known as decapping, performed complex composed Dcp2 catalytic subunit its partner Dcp1....
Plasmodium falciparum is the main cause of disease and death from malaria. P. virulence resides in ability infected erythrocytes (IEs) to sequester various tissues through interaction between members polymorphic erythrocyte membrane protein 1 (PfEMP1) adhesin family host receptors. Here, we investigated effect phosphorylation variant surface antigen 2-CSA (VAR2CSA), a member PfEMP1 associated placental sequestration, on its capacity adhere chondroitin sulfate A (CSA) present syncytium. We...
Abstract Allosteric modulation of pentameric ligand-gated ion channels (pLGICs) is critical to the action neurotransmitters and many psychoactive drugs. However, details their modulatory mechanisms remain unclear, especially beyond orthosteric neurotransmitter-binding sites. The recently reported prokaryotic channel sTeLIC, a pH-gated homolog eukaryotic receptors in pLGIC family, thought be modulated by aromatic compounds via relatively uncharacterized site extracellular vestibule. Here, we...
The nurse-scheduling is a common problem in hospitals. requires timetable considering hospital regulations and nurses' demands preferences. This study proposes an integrated Lexicographic goal programming dynamic satisfaction function model for solving problems. proposed provides the head nurses with balanced fair automated schedule. considers two aspects related to regulation constraints. First, aspect allows decision-makers integrate their judgment changing circumstances caused by nurse...
GLIC is a bacterial homologue of the pentameric ligand-gated ion channels (pLGICs) that mediate fast chemical neurotransmission nerve signalling in eukaryotes. Because activation and allosteric modulation features are conserved among prokaryotic eukaryotic pLGICs, commonly used as model to study transition structural pharmacology pLGICs. It has previously been shown inhibited by some carboxylic acid derivatives. Here, experimental evidence for carboxylate binding provided solving its X-ray...
Introduction: Conjugation is an excellent natural mode of DNA transfer in vivo between bacteria, particularly when these conjugative elements carry technological traits such as bacteriocin encoding genes. In the present work, bacteriocinogenic plasmid pIBF4 from Bacillus thuringiensis responsible Bacthuricin F4 synthesis was isolated and characterized. Methodology: To isolate pIBF4, total a non-bacteriocin transposant carrying mini-Tn10 spectinomycin selective marker extracted used to...