A5063144693- Complement system in diseases
- Proteoglycans and glycosaminoglycans research
- Virus-based gene therapy research
- Glycosylation and Glycoproteins Research
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Carbohydrate Chemistry and Synthesis
- Platelet Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- RNA Interference and Gene Delivery
- Invertebrate Immune Response Mechanisms
- Pharmacological Effects of Natural Compounds
- Protein Interaction Studies and Fluorescence Analysis
- Fibroblast Growth Factor Research
- Monoclonal and Polyclonal Antibodies Research
- Viral Infections and Vectors
- Viral Infections and Outbreaks Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- SARS-CoV-2 and COVID-19 Research
- Galectins and Cancer Biology
- Biomarkers in Disease Mechanisms
- Pneumonia and Respiratory Infections
- interferon and immune responses
- Viral gastroenteritis research and epidemiology
Université Grenoble Alpes
2014-2024
Institut de Biologie Structurale
2014-2024
CEA Grenoble
2011-2024
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2014-2024
Centre National de la Recherche Scientifique
2014-2024
Université Joseph Fourier
1990-2013
European Molecular Biology Laboratory
1997
Laboratoire Physiologie Cellulaire & Végétale
1990
Abstract Interferon-γ (IFNγ) is an important mediator of cellular immune responses, but high systemic levels this cytokine are associated with immunopathology. IFNγ binds to its receptor (IFNγR) and extracellular matrix (ECM) via four positively charged C-terminal amino acids (KRKR), the ECM-binding domain (EBD). Across evolution, not well conserved, EBD highly suggesting a critical function. Here, we show that lacking (IFNγ ΔKRKR ) does bind ECM still IFNγR retains bioactivity....
Ficolins are oligomeric innate immune recognition proteins consisting of a collagen-like region and fibrinogen-like domain that bind to pathogen- apoptotic cell-associated molecular patterns. To investigate their carbohydrate binding specificities, serum-derived L-ficolin recombinant H- M-ficolins were fluorescently labeled, ability was analyzed by glycan array screening. preferentially recognized disulfated N-acetyllactosamine tri- tetrasaccharides containing terminal galactose or...
Virus-like particles (VLPs) are highly suited platforms for protein-based vaccines. In the present work, we adapted a previously designed non-infectious adenovirus-inspired 60-mer dodecahedric VLP (ADDomer) to display multimeric array of large antigens through SpyTag/SpyCatcher system. To validate platform as potential COVID-19 vaccine approach, decorated newly with glycosylated receptor binding domain (RBD) SARS-CoV-2. Cryoelectron microscopy structure revealed that up 60 copies this...
Abstract Ficolins and pentraxins are soluble oligomeric pattern-recognition molecules that sense danger signals from pathogens altered self-cells might act synergistically in innate immune defense maintenance of tolerance. The interaction M-ficolin with the long pentraxin 3 (PTX3) has been characterized using surface plasmon resonance spectroscopy electron microscopy. was shown to bind PTX3 high affinity presence calcium ions. abolished EDTA inhibited by N-acetyl-D-glucosamine, indicating...
Ficolins are soluble oligomeric proteins with lectin-like activity, assembled from collagen fibers prolonged by fibrinogen-like recognition domains. They act as innate immune sensors recognizing conserved molecular markers exposed on microbial surfaces and thereby triggering effector mechanisms such enhanced phagocytosis inflammation. In humans, L- H-ficolins have been characterized in plasma, whereas a third species, M-ficolin, is secreted monocytes macrophages. To decipher the underlying...
Complement receptor type 1 (CR1) is a membrane expressed on wide range of cells. It involved in immune complex clearance, phagocytosis, and complement regulation. Its ectodomain composed 30 control protein (CCP) modules, organized into four long homologous repeats (A-D). In addition to its main ligands C3b C4b, CR1 was reported interact with C1q mannan-binding lectin (MBL) likely through C-terminal region (CCP22-30). To decipher the interaction human recognition proteins pathway, recombinant...
Sulfs represent a class of unconventional sulfatases which provide an original post-synthetic regulatory mechanism for heparan sulfate polysaccharides and are involved in multiple physiopathological processes, including cancer. However, remain poorly characterized enzymes, with major discrepancies regarding their vivo functions. Here we show that human Sulf-2 (HSulf-2) harbors chondroitin/dermatan glycosaminoglycan (GAG) chain, attached to the enzyme substrate-binding domain. We demonstrate...
The role of glycosaminoglycans (GAGs) in modulating bone morphogenetic protein (BMP) signaling represents a recent and underexplored area. Conflicting reports suggest dual effect: some indicate positive influence, while others demonstrate negative impact. This duality suggests that the localization GAGs (either at cell surface or within extracellular matrix) specific type GAG may dictate their role. precise sulfation patterns heparan sulfate (HS) responsible for BMP2 binding remain elusive....
Adenovirus penton base protein is involved in virus internalization. Searching for the cellular partners of this protein, we used dodecahedra, adenovirus subviral particles composed 12 bases, screening a human lung expression library. This screen yielded three ubiquitin−protein ligases, WWP1, WWP2, and AIP4, all which belong to HECT family contain multiple WW domains. The xPPxY motif, known interact with domains partner proteins occurs twice N-terminal part polypeptide chain. recruitment...
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies. Antibodies against Ficolin-3 were previously identified in sera some SLE patients, but their prevalence and significance have not been yet investigated. The aims this study to determine anti-ficolin-3 antibodies among patients investigate potential as diagnostic and/or prognostic biomarkers SLE. In retrospective study, from (n = 165) selected preexisting declared...
Poneratoxin is a small neuropeptide found in the venom of ant Paraponera clavata . It stored reservoir as an inactive 25‐residue peptide. Here we describe both chemically synthesized poneratoxin and obtained by expression insect cells. When expressed cells, was observed attached to cell membranes. Both synthetic recombinant ponerotoxins were soluble below pH 4.5. The structure characterized circular dichroism solved nuclear magnetic resonance. In environment imitating lipid bilayer, at...
Human L-ficolin is a soluble protein of the innate immune system able to sense pathogens through its fibrinogen (FBG) recognition domains and trigger activation lectin complement pathway associated serine proteases. L-Ficolin has been previously shown recognize pneumococcal clinical isolates, but ligands especially molecular specificity remain be identified. Using solid-phase binding assays, serum recombinant L-ficolins were interact with serotype 2 strain D39 unencapsulated R6 derivative....
ABSTRACT Ebola virus infection requires the surface viral glycoprotein to initiate entry into target cells. The trimeric is a highly glycosylated protein which has been shown interact with host C-type lectin receptors and soluble complement recognition mannose-binding lectin, thereby enhancing infection. Similarly ficolins are effectors of innate immune system that recognize particular glycans at pathogen surface. In this study, we demonstrate ficolin-1 interacts Zaire (EBOV) glycoprotein,...
Direct protein transduction is a recent technique that involves use of peptide vectors. In this study, we demonstrate adenovirus dodecahedron (Dd), virus-like particle devoid DNA and able to penetrate cells with high efficiency, can be used as vector for delivery.Taking advantage Dd interaction structural domains called WW, have elaborated universal adaptor attach interest vector.A tandem three WW derived from the Nedd4 enables formation stable complexes Dd, without impairing its endocytosis...
Abstract The BAG family of Hsp70/Hsc70 co‐chaperones is characterised by the presence a conserved domain at carboxyl‐terminus. BAG3 protein only member this containing also N‐terminally located WW domain. We describe here identification adenovirus (Ad) penton base as first partner recognising Ad viral capsid constituent responsible for virus internalisation. It contains in N‐terminal part two PPxY motifs, known ligands domains. In cells producing protein, cytoplasmic endogenous interacts...
Adenovirus dodecahedron is a virus-like particle composed of only two viral proteins human adenovirus serotype 3 that are responsible for virus attachment and internalization. We show here this dodecameric particle, devoid genetic information, efficiently penetrates cells can deliver large multimeric such as immunoglobulins.
Systemic lupus erythematosus (SLE) is a multisystem inflammatory disease characterized by the production of various autoantibodies. The aim this study was to investigate presence anti-ficolin-2 antibodies in SLE patients and evaluate association between levels these autoantibodies, clinical manifestations, activity.This comparative using cohort 165 48 healthy subjects. were further divided into 2 groups (low activity [SLE Disease Activity Index (SLEDAI) score ≤4, n = 88] high [SLEDAI >4,...
ABSTRACT M-ficolin specificity for sialylated ligands prompted us to investigate its interactions with the main membrane sialoprotein of human neutrophils, CD43. rM-ficolin bound CD43 and prevented access anti-CD43 mAb. Moreover, reacted exclusively on Western blots neutrophil lysate. We confirmed that is secreted by fMLP-activated this endogenous also binds competes Anti-CD43 antibody cross-linking or fMLP resulted in colocalization polarized neutrophils. The binding resting neutrophils...
Phosphocholine (PC) is an abundant primary form of organic phosphate that transported in plant xylem sap. Addition PC to the perfusate compressed Pi-starved sycamore cells monitored by 31P NMR spectroscopy resulted accumulation and all other esters cytoplasmic compartment. hemicholinium-3, inhibitor choline uptake, inhibited but not inorganic (Pi). When were perfused with a medium containing either Pi or PC, resulting distribution cell was same. instead compartment from kinase activity. In...
Human type 3 adenovirus dodecahedron (a virus like particle made of twelve penton bases) features the ability to enter cells through Heparan Sulphate Proteoglycans (HSPGs) and integrins interaction is used as a versatile vector deliver DNA or proteins. Cryo-EM reconstruction pseudoviral with (HS) oligosaccharide shows an extradensity on RGD loop. A set mutants was designed study respective roles sequence (RGE mutant) basic located just downstream. Results showed that RGE mutant binding HS...