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Cob4SAM: Deciphering the mechanistic and structural diversity of B12-dependent radical SAM enzymes – Cob4SAM
Radical SAM enzymes are arguably the largest and most functionally diverse enzyme superfamily with more than 500,000 enzymes predicted to be involved in more than 80 different types of biochemical transformations. These metalloenzymes catalyze chemically challenging reactions some of them having no
Microtubule subversion by VgrG2b, a Pseudomonas aeruginosa Type 6 secretion effector – Microb6
Main issues raised & general objectives : (number of characters : 0/3000) P. aeruginosa can invade non-phagocytic cells. We have shown that the VgrG2b effector is delivered by the type VI secretion machinery (T6SS) into the host where it targets the gamma-tubulin complex responsible for microtubul
Puzzling out the role of plant and fungal laccases with auxiliary enzymes during polymerization and depolymerization of lignin in a polysaccharide environment – DEOX
Lignin is a complex phenolic polymer embedded into the polysaccharide matrix of the plant cell wall. The lignin deposition makes the plant biomass highly recalcitrant to human utilization. Interestingly, the polymerization of lignin in the plant cell wall and the depolymerization of lignin by microo
Structures and translocation process of CyaA – 3DTransCyaA
Protein transport across membranes involves complex translocation machineries. Most proteins and toxins exploit the endocytosis machinery and intracellular sorting to gain access to target cell compartments, while few others, such as the adenylate cyclase CyaA toxin, carry their own translocation ap
Transkingdom structural and functional characterization of amyloid signalosomes – TransKingAmyloid
Signalosomes are high-order molecular machines involved in activation and execution of programmed cell death in immunity. Termed apoptosomes/inflammasomes in mammals and resistosomes in plants, their assembly can be driven by the aggregation of amyloids in large suprastructures. We recently uncovere
Interplay of DNA topology and transcription – TOPORNAP
Transcription of DNA to RNA, the first step in the expression of genetic information, requires tight regulation. As a consequence, misregulation leads to severe diseases. Furthermore, the key enzymes involved in transcription are some of the most important drug targets. Transcription causes and is a
Energy dependent iron import by Gram-negative bacteria: deciphering the molecular mechanism by an integrative approach – Energir
Gram-negative bacteria are delimited by an envelope composed of two membranes (the outer and the inner membranes) separated by the periplasmic space. This envelope includes macromolecular machines that ensure and regulate exchanges between the bacterium and its environment. In contrast to small mole
Apolipoprotein AI Mimetic Peptide lipid Asemblies – AAMLA
Research context & theoretical framework: Chronic inflammation, cancer and atherosclerosis are leading causes of death worldwide being associated with oxidative stress. Apolipoprotein AI (apo-AI) mimetic peptides (AAMs) are a new class of therapeutics that possess anti-oxidant and anti-inflammator
Prion Domains in Plant Environmental Response – PROSPERO
Plants adapt to the environment by adjusting their development in response to cues including light and temperature. This enables them to anticipate stresses, respond via changes in their growth and development and optimize their survival and reproductive success under varying environmental condition
Structural Dynamics of Photoinduced Gene Regulation – PhotoGene
Photoreceptor proteins regulate adaptation of living organisms to light. A class recently discovered uses a vitamin B12 derivative to sense green light and regulate the biosynthesis of carotenoids, which protect against photo-oxidative damage. CarH is a prototype of this class. Its sophisticated mac
COPLAnAR: COrrelative investigations of PLAnt cuticle ARchitecture associated to its functionalities – COPLAnAR
Plant cuticles are complex hydrophobic edifices of lipid (cutin, a polyester of hydroxy fatty acids) and carbohydrate polymers (pectin, cellulose). They play a major role in the development of plants and their resistance to environmental stresses, and are now considered as major targets for the bree
Dynamics, nanoscale organization and modeling of LINC under mechanical stress – DynamoLINC
In response to mechanical cues, the cell nucleus regulates critical processes such as cell migration, cell fate, gene expression and cell differentiation. At the nuclear envelope, the Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes serve as crucial mechanotransducing hubs. Yet, the nanosc
Structure and impact of lipids on the 5-HT2A-mGlu2 heteromer, a schizophrenia drug target – Schizoceptor
Schizophrenia is a severe neuropsychiatric disorder affecting 1% of humans. G protein coupled receptors (GPCRs) are its main medication target but drugs fail to address all symptoms and trigger side effects, stressing the need for new research. Recently, two GPCRs, the metabotropic glutamate mGlu2 a
Targeting Myosin : understanding and tuning force production for therapy development – MYODRUG
Myosins are molecular motors that play pivotal roles in all the processes of life. Mutations in distinct classes of myosins lead to diseases. Small molecules able to modulate the force produced by such motors are currently in clinical trials with promising results for distinct muscle diseases, notab
Deciphering the role of adhesion dynamics in synapse development using micropatterning and multimodal microscopy – Synaptoligation
Adhesion is a fundamental property in cell biology, regulating many processes including cell shape and differentiation. At the molecular level, adhesion is mediated by specific membrane-associated ligand-receptor pairs. Several families of adhesion molecules, including the neurexin-neuroligin comple
Protein-lipid functional interactions characterized with a new generation of amphipathic polymers – PROLIFIC
One of the emerging features of the protein-lipid interactome is that certain lipid molecules can selectively bind to specific sites on membrane proteins (MPs) playing key roles in folding and stability of MPs or acting as allosteric regulators of protein function. The tools to study these interacti
in vitro reconstitution of the minimal flippase-operated phospholipid transport machinery – FLIPPER
The asymmetric distribution of lipids between the two leaflets of cell membranes is a fundamental feature of eukaryotic cells. For instance, while phosphatidylcholine and sphingomyelin are restricted to the outer leaflet of membranes of the late secretory/endocytic pathways in most cell types, phosp
Revealing the mechanism of action of large intrinsically disordered scaffold proteins in MAPK cell signaling – ScaffoldDisorder
Mitogen-activated protein kinases (MAPKs) are components of eukaryotic signal transduction networks. Intrinsically disordered scaffold proteins play crucial roles in ensuring signaling specificity by assembling multiple kinases into dynamic signaling complexes. This assembly leads to sequential acti
Lipid and protein dynamics in lipid droplet assembly – LIPRODYN
Lipid droplets (LDs) are cellular organelles resembling oil-in-water emulsion droplets, containing neutral lipids, coated by phospholipids and proteins. LDs are responsible for regulation of energy and lipid metabolism, and deficiencies in their formation or functioning lead to disease. Generated in
Deciphering the architecture and function of bacterial membrane metal efflux platforms – BAC-MMEP
Metal ions are toxic in large quantities and their intracellular concentration must be finely regulated. We have previously found that metals are used by macrophages to poison the tuberculosis bacillus, Mycobacterium tuberculosis (Mtb), and that metal efflux pumps of the P-ATPase superfamily are req
Ultrafast structural dynamics of Archaerhodopsin-3 in its fluorescent state – ULTRArchea
Archaerhodopsin-3 (AR-3), a photo-activated proton pump from Halorubrum sodomense, is the progenitor of an entire class of genetically encoded fluorescent membrane voltage indicators (GEVI). Like in other microbial rhodopsins, absorption of visible light triggers in AR-3 the retinal chromophore reve
DNA-synthesis coupled histone assembly by the chaperone CAF-1 – CAFinDS
Les modifications post-transcriptionnelles des histones, les variants et les protéines se liant aux histones constituent, en plus de la séquence des gènes, une information supplémentaire. Cette information contribue à la régulation de l'accessibilité de l'ADN, et à la programmation de l’identité cel
Structure-function analysis of a prominent target in fibrosis: the C-terminal maturation complex of fibrillar collagens – Pcube_complex
Fibrillar collagens are the most abundant proteins in the human body and any defect in their biosynthesis or the disruption of the balance between their synthesis and degradation cause major pathological disorders. These include rare genetic diseases such as osteogenesis imperfecta and numerous debi
Molecular mechanism of insecticide action at pentameric receptors – Pesti-Penta
While insecticides are essential tools in agriculture, their effects on ecosystems are deleterious. One third of insecticides (e.g. neonicotinoids, fipronil and broflanilide) act by targeting insect pentameric ligand-gated ion channels. The project aims to understand the molecular mode of action of
Mechanism and function of protein glutamylation during Legionella infection – BACTGLU
Legionella pneumophila secretes ~300 effector proteins into the host cytosol during infection. These effectors exert multitude of biochemical activities and drive the maturation of Legionella containing vacuole (LCV) by hijacking several host defense pathways. Deletion of the effector SidJ negativel
Phase separations and transitions by Henipavirus V and W proteins: molecular mechanisms and implications for functions and pathogenesis – HENIPHASE
The Nipah and Hendra viruses (NiV & HeV) (Henipavirus genus) are zoonotic pathogens responsible for severe encephalitis in humans. Their natural reservoir are fruit bats. Inter-human transmission of NiV and circulation of Henipaviruses in bat species from a growing number of countries, constitute a
Fingerprinting of Glycosaminoglycans by Single Molecule Nanopore Sensing: Towards a sequencing tool for Glycosaminoglycomics – GAGS-NANOSENSOR
The project aims at providing the first analytical method at the single molecule level for the sequencing of bioactive glycosaminoglycan polysaccharides by using the nanopore sensing, with immediate applicability in biological and pathophysiological research, especially for diagnostic and identifica
Dynamics and nanoscale topology of the membrane-associated Rab11-vRNP complex in the context of influenza virus-infected cells – FluNanoTrack
Influenza A viruses (IAV) pose a serious threat to global public health. Development of improved influenza prevention and therapy, whether it be the universal vaccine or novel anti-influenza drugs, will depend strongly on fundamental science improving our understanding of the molecular mechanisms in
Extracellular Vesicle Delivery through membrane Fusion – EVfusion
Over the last decade, Extracellular Vesicles (EVs), including Exosomes, emerged as an important vector of intercellular communication. EVs have been proposed to transfer cargoes such as lipids, nucleic acids and proteins from donor to acceptor tissues or cells. EVs have been associated with several
Structure/function analysis of the Com pilus, a widespread filamentous nanomachine dedicated to DNA uptake in monoderm bacteria – ComPil
Transformation – a mode of horizontal gene transfer (HGT) widespread in bacteria – is defined as the ability of bacteria to bind free DNA, translocate it across membrane(s), and recombine it in the recipient’s genome. Because HGT can have dramatic consequences on human health, such as transmission o
Mechanism of TBP delivery to gene promoters by the SAGA co-activator – SAGA-TBP
Transcription initiation is an essential step in gene regulation, which allows organisms to adapt to external changes. To initiate transcription, the TATA-box binding protein TBP has to be delivered in a highly controlled way to promoters of protein encoding genes. The interaction of TBP with the pr
Deep contrast-variation SAXS: a new tool for structural biology – DeepSAXS
Small-angle X-ray scattering (SAXS) has become an essential technique in the structural biologist’s toolbox. It provides valuable information on the shape, size, flexibility and molecular mass of biomacromolecules in solution as well as complementary restraints to crystallography, NMR and (cryo-)EM.
Nucleosome Invasion Mechanism of the Sox Pioneer Transcription Factor family – SIMOS
The pioneer transcription factors Sox are characterized by a highly conserved HMG DNA-binding domain that recognizes a consensus TTGT core motif. Sox-HMG binds to DNA by widening the minor groove while inducing a sharp bend in the DNA flanking the core motif. Cryo-EM structures have recently been re
Structure and function of the targeting machinery for nuclear RNA degradation. – MTREC
Research in the RNA field over the last years has revealed that an astonishing amount of RNA, including a sizeable portion of aberrant transcripts, is constantly being synthesized within eukaryotic nuclei. To detect and eliminate specific or aberrant transcripts, cells rely on highly regulated RNA d
Unraveling molecular interactions between wine lactic acid bacteria, their viral predators, and polyphenols – WINE
Lactic acid bacteria (LAB)-infecting bacteriophages (phages, or bacterial viruses) use diverse host-binding mechanisms, yet the overall picture of the interactions between LAB phages and their host remains incomplete. Unraveling the molecular details of phage-LAB interactions is essential not only f
Archaeal roots of eukaryotic class II membrane fusion proteins – ArcFus
Class II membrane fusion proteins have been identified in diverse enveloped viruses (e.g., Zika, chikungunya) as well as in organisms belonging to four of the five eukaryotic kingdoms, where they perform gamete fusion during fertilization. Our bioinformatics analyses suggest an ancestral origin of t
Mechanistic characterization of in vitro reconstituted bacterial cell division subcomplexes – MecaDiv
Bacterial cell division is a temporally and spatially regulated process coordinated by a multi-protein complex called the divisome. The assembly of the divisome is initiated and organized by a highly conserved bacterial protein, the bacterial tubulin homologue FtsZ, which polymerizes to form a dynam
Unraveling the role of AURKA on mitochondria cristae structure by super-resolution microscopy and FRET – MACSUP
Mitochondria, the powerhouse of the cell, are double-membrane organelles. While the outer membrane encloses mitochondria, the inner one is folded into invaginations called cristae. Long considered static structures, recent data revealed that cristae are rather dynamic. However, the molecular players
Tropomyosins and differentiation of actin filament networks – TropActin
Within a single cell, the actin cytoskeleton forms diverse networks of filaments, implicated in many fundamental functions. These actin networks are assembled from a common pool of actin and regulatory proteins, but how network differentiation is regulated has remained a very challenging question fo
Deciphering the molecular causation of human acute promyelocytic leukemia (APL), an innovative approach to improve treatment of retinoid-sensitive malignancies – RepreX
In the absence of its cognate ligand (retinoic acid, ATRA), retinoic acid receptor alpha (RARa) acts as a transcriptional repressor by recruiting corepressor (CoR) complexes to target genes. This constitutive repression is crucial in metazoans. However, its specific molecular determinants remain obs
Structure and mechanics of composite cytoskeletal networks – CoCyNet
Cytoskeletal networks are largely responsible for the mechanical properties of living cells, and are composed of three types of interconnected biopolymers: actin, intermediate filaments (IFs) and microtubules. Among those, actin filaments and microtubules form dynamic networks that can quickly assem