Elian Dupré

Université de Lille · Department of Biology

Since end of 2019, the global and unprecedented outbreak caused by the coronavirus SARS-CoV-2 led to dramatic numbers of infections and deaths worldwide. SARS-CoV-2 produces two large viral polyproteins which are cleaved by two cysteine proteases encoded by the virus, the 3CL protease (3CLpro) and the papain-like protease, to generate non-structura...

Protein aggregation into highly ordered, regularly repeated cross-β sheet structures called amyloid fibrils is closely associated to human disorders such as neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases, or systemic diseases like type II diabetes. Yet, in some cases, such as the HET-s prion, amyloids have biological func...

The accumulation of pathological Tau in the brain and cerebrospinal fluid (CSF) and its eventual increase in the blood are hallmarks of Alzheimer’s disease (AD). However, the mechanisms of Tau clearance from the brain to the periphery are not clear. We show here, using animal and cellular models as well as patient blood samples and post mortem brai...

Tau proteins aggregate into filaments in brain cells in Alzheimer’s disease and related disorders referred to as tauopathies. Here, we used fragments of camelid heavy-chain-only antibodies (VHHs or single domain antibody fragments) targeting Tau as immuno-modulators of its pathologic seeding. A VHH issued from the screen against Tau of a synthetic...

Tau proteins aggregate into filaments in brain cells in Alzheimer's disease and related disorders referred to as tauopathies. Here, we used fragments of camelid heavy-chain-only antibodies (VHHs or single domain antibody fragments) targeting Tau as immuno-modulators of its pathologic seeding. A VHH issued from the screen against Tau of a synthetic...

The two-component system BvgAS controls the virulence regulon in Bordetella pertussis . BvgS is the prototype of a family of sensor histidine-kinases harboring periplasmic Venus flytrap (VFT) domains. The VFT domains are connected to the cytoplasmic kinase moiety by helical linkers separated by a Per-ARNT-Sim (PAS) domain. Antagonism between the tw...

Tau is a neuronal protein linked to pathologies called tauopathies, including Alzheimer’s disease. In Alzheimer’s disease, tau aggregates into filaments leading to the observation of intraneuronal fibrillary tangles. Molecular mechanisms resulting in tau aggregation and in tau pathology spreading through the brain regions are still not fully unders...

Although Tau is an intrinsically disordered protein, some level of structure can still be defined, corresponding to short stretches of dynamic secondary structures and a preferential global fold described as an ensemble of conformations. These structures can be modified by Tau phosphorylation, and potentially other post-translational modifications....

Bordetella pertussis controls the expression of its virulence regulon through the two-component system BvgAS. BvgS is a prototype for a family of multidomain sensor kinases. In BvgS, helical linkers connect periplasmic Venus flytrap (VFT) perception domains to a cytoplasmic Per-Arnt-Sim (PAS) domain and the PAS domain to the dimerization/histidine...

The whooping cough agent, Bordetella pertussis, controls the expression of its large virulence regulon in a coordinated manner through the two-component system BvgAS. BvgS is a dimeric, multidomain sensor kinase. Each monomer comprises, in succession, tandem periplasmic Venus flytrap (VFT) domains, a transmembrane segment, a cytoplasmic Per-Arnt-Si...

The two-component system BvgAS controls the expression of the virulence regulon of Bordetella pertussis. BvgS is a prototype of bacterial sensor kinases with extracytoplasmic Venus flytrap perception domains. Following its transmembrane segment, BvgS harbors a cytoplasmic Per-Arnt-Sim (PAS) domain and then a predicted 2-helix coiled coil that prece...

Detection of the inactive BvgS variants in B. pertussis. Immunoblot analyses of BvgS variants (indicated by an arrow) in membrane extracts of B. pertussis with no or little activity. The avirulent, ΔbvgA strain was used as a control to show the abundance of BvgS in an avirulent strain. The loading control is an unidentified B. pertussis protein for...

Supplemental methods. Construction of the plasmids used in this work. Protein sequence analyses. Download

Characterization of the BvgS Cys variants. (A) Intradimer S-S formation for BvgSt with its two natural Cys residues (WT) and for its variants harboring the Cys607Ala-plus-Cys881Ser, Cys607Ala, or Cys881Ser substitution under basal conditions (−) or after the addition of 5 mM chloronicotinate (+). The monomeric and dimeric forms of the BvgSt variant...

Deletion of the PAS domain affects BvgS function. (A) Sequence alignment of the three BvgS variants harboring deletion of the PAS domain and the wt BvgS. Note that in the variants, the Glu701 residue of BvgS was replaced with Gly, as in sensor kinase PP3413 of Pseudomonas putida. (B) Determination of the activities of BvgS variants harboring PAS de...

Activities of specific variants using the fhaB-lacZ reporter system. (A) BvgS variants with Ala-to-Leu substitutions. (B) BvgSΔPAS-R1 variants. The means and standard errors of the means are given. Download

Interaction energies of 2-HCC in PAS-less BvgS variants determined in silico. The average values of pseudoenergy of interaction per residue were calculated from 10 models of coiled coil for each variant (ΔPAS-R1 to -R4), and the errors of the means are given. Download

The two-component sensory transduction system BvgAS controls the virulence regulon of the whooping-cough agent Bordetella pertussis. The periplasmic moiety of the homodimeric sensor kinase BvgS is composed of four bilobed Venus flytrap (VFT) perception domains followed by α helices that extend into the cytoplasmic membrane. In the virulent phase, t...

The two-component sensory transduction system BvgAS controls the virulence regulon of the whooping-cough agent Bordetella pertussis. The periplasmic moiety of the homo-dimeric sensor-kinase BvgS is composed of four bilobed Venus flytrap (VFT) perception domains followed by α helices that extend into the cytoplasmic membrane. In the virulent phase,...

Two-component systems (TCS) represent major signal-transduction pathways for adaptation to environmental conditions, and regulate many aspects of bacterial physiology. In the whooping cough agent Bordetella pertussis, the TCS BvgAS controls the virulence regulon, and is therefore critical for pathogenicity. BvgS is a prototypical TCS sensor-kinase...

TpsB proteins are Omp85 superfamily members that mediate protein translocation across the outer membrane of Gram-negative bacteria. Omp85 transporters are composed of N-terminal POTRA domains and a C-terminal transmembrane β-barrel. In this work, we track the in vivo secretion path of the Bordetella pertussis filamentous haemagglutinin (FHA), the s...

Virulence of Bordetella pertussis, the whooping cough agent, is due to a plethora of virulence factors which expression is regulated by the two-component system BvgAS. BvgA is a classical response regulator and BvgS the sensor. BvgS contains 3 putative sensor domains, 2 periplasmic Venus FlyTrap (VFT), linked through a transmembrane segment to a cy...

In bacteria, signal-transduction two-component systems are major players for adaptation to environmental stimuli. The perception of a chemical or physical signal by a sensor-kinase triggers its autophosphorylation. The phosphoryl group is then transferred to the cognate response regulator, which mediates the appropriate adaptive response. Virulence...

Two-component sensory transduction systems control important bacterial programs. In Bordetella pertussis, expression of the virulence regulon is controlled by the unorthodox BvgAS two-component system. BvgS is the prototype of a family of sensor-kinases that harbor periplasmic domains homologous to bacterial solute-binding proteins. Although BvgAS...