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Toxin membrane interactions

Daniel Gillet
CEA Saclay / Bât. 152

Tél : 01 69 08 76 46


Moyens humains
Julien BARBIER, Researcher
Daniel GILLET, Group Leader
Sylvain PICHARD, Research Technician
Amélie GOUDET, Research Technician
Céline BOUCLIER, Post-doctoral Fellow
Benoit VILLIERS, Post-doctoral Fellow
Anne ARAYE-GUET, PhD Student

Thèmes de recherche

The focus of our work is the mechanism by which bacterial toxins, in particular diphtheria and botulinum toxins, cross biological membranes and infect cells. We are investigating at the sub-molecular level conformational changes of the toxin translocation domains during their interaction at acid pH with membrane models.
We are developing biotechnological applications derived from bacterial toxins as well as animal and plant toxins. These applications concern the production of targeted toxin and anti-cancer vaccines. We are searching for botulinum toxins and ricin inhibitors by high throughput screening using cellular functional assays.

 Toxine Diphtérique
Toxine Botulique
© CEA / D. Gillet
© CEA / D. Gillet



Almunia C, Bretaudeau M, Held G, Babon A, Marchetti C, Castelli FA, Menez A, Maillère B, Gillet D. (2013). Bee Venom Phospholipase A2, a Good "Chauffeur" for Delivering Tumor Antigen to the MHC I and MHC II Peptide-Loading Compartments of the Dendritic Cells: The Case of NY-ESO-1. PLoS ONE, 8(6):e67645.

Ming X, Carver K, Fisher M, Noel R, Cintrat JC, Gillet D, Barbier J, Cao CH, Bauman J, Juliano RL. (2013). The small molecule Retro-1 enhances the pharmacological actions of antisense and splice switching oligonucleotides. Nucleic Acids Res., 41, 3673-3687.

Noel R, Gupta N, Pons V, Goudet A, Garcia-Castillo MD, Michau A, Martinez J, Buisson DA, Johannes L, Gillet D, Barbier J, Cintrat JC. (2013). N-Methyldihydroquinazolinone Derivatives of Retro-2 with Enhanced Efficacy against Shiga Toxin. J. Med. Chem., 56, 3404-3413.

Barbier J, Bouclier C, Johannes L, Gillet D. (2012). Inhibitors of the Cellular Trafficking of Ricin. Toxins. 4, 15-27.

Chassaing A, Pichard S, Araye-Guet A, Barbier J, Forge V, Gillet D. (2011). Solution and membrane-bound chaperone activity of the diphtheria toxin translocation domain towards the catalytic domain. FEBS J. 278, 4516-4525.

Laverroux S, Glasser F, Gillet M, Joly C, Doreau M. (2011). Isomerization of Vaccenic Acid to cis and trans C18:1 Isomers During Biohydrogenation by Rumen Microbes. Lipids. 46, 843-850.

Man P, Montagner C, Vitrac H, Kavan D, Pichard S, Gillet D, Forest E, Forge V. (2011). Accessibility Changes within Diphtheria Toxin T Domain upon Membrane Penetration Probed by Hydrogen Exchange and Mass Spectrometry. J Mol Biol. 414, 123-134.

Man P, Montagner C, Vitrac H, Kavan D, Pichard S, Gillet D, Forest E, Forge V. (2010). Accessibility changes with diphteria toxin T domain when in the functional molten globule state, as determined using hydrogen/deuterium exchange measurements. FEBS J., 277, 653-662.

Stechmann B, Bai S K, Gobbo E, Lopez R, Merer G, Pinchard S, Panigai L, Tenza D, Raposo G, Beaumelle B, Sauvaire D, Gillet D, Johannes L, Barbier J. (2010). Inhibition of Retrograde Transport Protects Mice from Lethal Ricin Challenge. Cell. 141, 231-242.

Aisenbrey C, Prongidi-Fix L, Chenal A, Gillet D, Bechinger B. (2009). Side Chain Resonances in Static Oriented Proton-Decoupled (15)N Solid-State NMR Spectra of Membrane Proteins. J Am Chem Soc.131, 6340-1.

Chenal A, Prongidi-Fix L, Perier A, Aisenbrey C, Vernier G, Lambotte S, Fragneto G, Bechinger B, Gillet D, Forge V, Ferrand M. (2009). Deciphering membrane insertion of the diphtheria toxin T domain by specular neutron reflectometry and solid-state NMR spectroscopy. J Mol Biol. 391, 872-883.

Galloux M, Vitrac H, Montagner C, Raffestin S, Popoff MR, Chenal A, Forge V, Gillet D. (2008). Membrane interaction of botulinum neurotoxin A T domain: The belt region is a regulatory loop for membrane interaction. J Biol Chem. 283, 27668-76.

Huang T, Nallathamby PD, Gillet D, Xu XH. (2007). Design and Synthesis of Single-Nanoparticle Optical Biosensors for Imaging and Characterization of Single Receptor Molecules on Single Living Cells. Anal Chem. 79, 7708-7718.

Montagner C, Perier A, Pichard S, Vernier G, Menez A, Gillet D, Forge V, Chenal A. (2007). Behavior of the N-Terminal Helices of the Diphtheria Toxin T Domain during the Successive Steps of Membrane Interaction. Biochemistry. 46, 1878-1887.

Perier A, Chassaing A, Raffestin S, Pichard S, Masella M, Ménez A, Forge V, Chenal A, Gillet D. (2007).Concerted protonation of key histidines triggers membrane interaction of the diphtheria toxin T domain. J Biol Chem. 282, 24239-24245.

Perier A, Gourier C, Pichard S, Husson J, Lajeunesse E, Babon A, Ménez A, Gillet D. (2007).Creation of intercellular bonds by anchoring protein ligands to membranes using the diphtheria toxin T domain. FEBS Lett. 581, 5480-5484.

Janjic B, Andrade P, Wang XF, Fourcade J, Almunia C, Kudela P, Brufsky A, Jacobs S, Friedland D, Stoller R, Gillet D, Herberman RB, Kirkwood JM, Maillere B, Zarour HM. (2006). Spontaneous CD4+ T cell responses against TRAG-3 in patients with melanoma and breast cancers. J Immunol. 177, 2717-2727.

Chenal A, Vernier G, Savarin P, Bushmarina NA, Geze A, Guillain F, Gillet D, Forge V. (2005). Conformational States and Thermodynamics of a-Lactalbumin Bound to Membranes: A Case Study of the Effects of pH, Calcium, Lipid Membrane Curvature and Charge. J Mol Biol. 349, 890-905.

Mandic M, Castelli F, Janjic B, Almunia C, Andrade P, Gillet D, Brusic V, Kirkwood JM, Maillere B, Zarour HM. (2005). One NY-ESO-1-derived epitope that promiscuously binds to multiple HLA-DR and HLA-DP4 molecules and stimulates autologous CD4+ T cells from patients with NY-ESO-1-expressing melanoma. J Immunol. 174, 1751-1759.

Menetrey J, Gillet D, Menez A. (2005). Structural features common to intracellularly acting toxins from bacteria. Toxicon. 45, 129-137.

Babon A, Almunia C, Boccaccio C, Beaumelle B, Gelb MH, Menez A, Maillere B, Abastado JP, Salcedo M, Gillet D. (2005). Cross-presentation of a CMV pp65 epitope by human dendritic cells using bee venom PLA2 as a membrane-binding vector FEBS Lett. 579, 1658-1664.

Barbier J, Lamthanh H, Le Gall F, Favreau P, Benoit E, Chen H, Gilles N, Ilan N, Heinemann SH, Gordon D, Menez A, Molgo J. (2004). A delta-conotoxin from Conus ermineus venom inhibits inactivation in vertebrate neuronal Na+ channels but not in skeletal and cardiac muscles. J Biol Chem. 279, 4680-4685.

Barbier J, Popoff MR, Molgo J. (2004). Degeneration and regeneration of murine skeletal neuromuscular junctions after intramuscular injection with a sublethal dose of Clostridium sordellii lethal toxin. Infect Immun. 72, 3120-3128.

Buhot C, Chenal A, Sanson A, Pouvelle-Moratille S, Gelb MH, Menez A, Gillet D, Maillere B. (2004). Alteration of the tertiary structure of the major bee venom allergen Api m 1 by multiple mutations is concomitant with low IgE reactivity. Protein Sci. 13, 2970-2978.

Tavallaie M, Chenal A, Gillet D, Pereira Y, Manich M, Gibert M, Raffestin S, Popoff MR, Marvaud JC. (2004). Interaction between the two subdomains of the C-terminal part of the botulinum neurotoxin A is essential for the generation of protective antibodies. FEBS Lett. 572, 299-306.

Volpon L, Lamthanh H, Barbier J, Gilles N, Molgo J, Menez A, Lancelin JM. (2004). NMR Solution Structures of {delta}-Conotoxin EVIA from Conus ermineus That Selectively Acts on Vertebrate Neuronal Na+ Channels. J Biol Chem. 279, 21356-21366.

Maillere B, Buhot C, Texier C, Pouvelle-Moratille S, Menez A, Gillet D. (2003). Modified peptides and recombinant proteins derived from the major bee venom allergen PLA2. Rev Fr Allergol Immunol Clin. 43, 53-55.

Mandic M, Almunia C, Vicel S, Gillet D, Janjic B, Coval K, Maillere B, Kirkwood JM, Zarour HM. (2003). The alternative open reading frame of LAGE-1 gives rise to multiple promiscuous HLA-DR-restricted epitopes recognized by T-helper 1-type tumor-reactive CD4+ T cells. Cancer Res. 63, 6506-6515.

Nizard P, Gross DA, Babon A, Chenal A, Beaumelle B, Kosmatopoulos K, Gillet D. (2003). Anchoring cytokines to tumor cells for the preparation of anticancer vaccines without gene transfection in mice. J Immunother. 26, 63-71.