Integrative Biological NMR
Group Leader
Group Leader
Our research focuses on the development of NMR methods and their applications, together with other biophysical techniques, in structural biology and to the biophysics of membranes, to characterize virulence factors or therapeutic targets associated with cancers or pathogen-host relationships, with a particular focus on mycobacterial infection.
An interdisciplinary research group elucidating molecular structure, dynamics, and interactions of biological processes using NMR, biophysical methods, and MD simulations.
The Integrative Biological NMR group applies its expertise and state-of-the-art equipment to pursue ambitious projects in structural biology with important implications in pharmacology. The study of structure, dynamics, and interactions of biomolecules are key to elucidating biochemical processes at atomic resolution. We continuously explore new avenues, such as the structure and function of complex membrane assemblies, and the influence of macromolecular dynamics on interactions, in the context of bacterial infection and cancer.
The relationship between host and pathogen is mediated by numerous biological processes. The molecular mechanisms by which the host detects and responds to infection by pathogens and by which pathogens circumvent host defences are of primary relevance to the development of novel therapeutic approaches.
– We are seeking to understand the defence mechanism of Mycobacterium tuberculosis against metal intoxication in human phagocytes, and to decipher the host’s response to pathogens mediated at a molecular level by a family of cell surface receptors. Upon infection by Mtb, macrophages attempt intoxication of the bacterium via an increase in the concentration of metals such as copper and zinc. In this context, the group of Dr. Olivier Neyrolles (IPBS) has identified three P1-type ATPases of Mtb (CtpC, CtpG and CtpV), each co-expressed with a small membrane-associated protein, PacL1, PacL2 and PacL3, respectively. While CtpC is required for optimal intracellular survival of Mtb at high zinc concentrations, PacL1 is required for zinc resistance in Mtb, it colocalises in foci with CtpC, and it stabilises CtpC efflux platforms at the plasma membrane. PacL1 therefore represents a novel type of metallochaperone in the sense that it binds zinc and stabilises CtpC. We are studying the selectivity of these metallochaperones towards metals and the mechanism of metal transfer towards the associated transporter.
– C-type lectin receptors (CLRs) are host proteins that play key roles in the innate immune system. CLRs allow cells to recognise characteristic molecules of pathogens or damaged cells and to trigger signalling pathways that culminate in protective effects. A better understanding of CLR signalling at the molecular level may facilitate the development of therapeutic agents targeting these receptors. Limited structural data is available, however, shedding only some light on ligand recognition. We focus specifically on a set of transmembrane CLRs (Mincle, Dectin-1, Dectin-2 and DCIR) that play key roles in pathologies such as infection, by Mtb and other bacteria, cancers, and autoimmune diseases. These CLRs are representatives of diverse signalling mechanisms. We aim to provide a detailed explanation of the allosteric coupling between extracellular ligand binding and intracellular partner protein recruitment that results in immune cell response.
Team members
Research Scientists
Andrew Atkinson (CNRS)
Georges Czaplicki (University)
Pascal Demange (CNRS)
Guillaume Ferré (University)
Evert Haanappel (CNRS)
Alain Milon (University)
Isabelle Muller (University)
Valérie Réat (CNRS)
Olivier Saurel (CNRS)
Research Engineers
Dunkan Bégué
Nathalie Doncescu (CNRS)
Yasmina Grimoire
Pascal Ramos (University)
PhD Students
Floriane Audebert
Louis Benastre
Maxime Noriega
Our research projects
Deciphering the architecture and function of bacterial membrane efflux platforms
Understanding immune cell signalling through C-type lectin receptors
Further collaborations
Ferré et al. (2023) Sodium is a negative allosteric regulator of the ghrelin receptor. Cell Rep
Schahl et al. (2022) Evidence for amylose inclusion complexes with multiple acyl chain lipids using solid-state NMR and theoretical approaches. Carbohydr Polym
Ferré et al. (2019) Structure and dynamics of G protein-coupled receptor-bound ghrelin reveal the critical role of the octanoyl chain. Proc Natl Acad Sci USA
Augenstreich et al. (2019) The conical shape of DIM lipids promotes Mycobacterium tuberculosis infection of macrophages. Proc Natl Acad Sci USA
Saurel et al. (2017) Local and global dynamics in Klebsiella pneumoniae outer membrane protein a in lipid bilayers probed at atomic resolution. J Am Chem Soc
Carel et al. (2017) Identification of specific posttranslational O-mycoloylations mediating protein targeting to the mycomembrane. Proc Natl Acad Sci USA
Macromolecular interactions by NMR: Solution structure of the THAP zinc finger of THAP1 in complex with its DNA target (PDB entry 2KO0). © Olivier Saurel
Institut de Pharmacologie et de Biologie Structurale (IPBS), Toulouse
Dr. Matthieu Chavent Multiscale Computational Immunology
Dr. Ahmed Amine Khamlichi Genetic Instability and Transcriptional Regulation
Dr. Lionel Mourey Structural Biophysics
Dr. Olivier Neyrolles Mycobacterial Interactions with Host Cells
Dr. Jérôme Nigou Immunomodulation by Mycobacterial Lipids and Glycoconjugates
G.CLIPS biotech
Dr. Rosie Dawaliby
Institut de Recherche en Santé Digestive (IRSD), Toulouse
Prof. Eric Oswald Pathogenesis and Commensalism of Enterobacteria
Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique (SPCMIB), Toulouse
Dr. Yves Génisson MoNALISA
Dr. Christian Lherbet SySMiC
Toulouse Biotechnology Institute (TBI), Toulouse
Dr. Didier Zerbib PHYGE – Integrated Physiology and Functional Genomics of
Microbial Systems
University of the Western Cape, South Africa
Prof. David J.R. Pugh Department of Biotechnology
Our laboratory is supported by grants from:
- Agence Nationale de la Recherche (ANR)
- Université de Toulouse III – Paul Sabatier
- Infrastructures en Biologie Santé et Agronomie (IBiSA)
- ERDF – REACT-EU
The complete list of our publications is available through Pubmed.
2023
Ferré, G., Gomes, A.A.S., Louet, M., Damian, M., Bisch, P., Saurel, O., Floquet, N., Milon, A., Banères, J.-L. (2023) Sodium is a negative allosteric regulator of the ghrelin receptor. Cell Rep in press
2022
Schahl, A., Lemassu, A., Jolibois, F., Réat, V. (2022) Evidence for amylose inclusion complexes with multiple acyl chain lipids using solid-state NMR and theoretical approaches. Carbohydr Polym 276, 118749
Pritzlaff, A., Ferré, G., Mulry, E., Lin, L., Gopal Pour, N., Savin, D.A., Harris, M.E., Eddy, M.T. (2022) Atomic-scale view of protein-PEG Interactions that redirect the thermal unfolding pathway of PEGylated human galectin-3. Angew Chem Int Ed Engl 61, e202203784
Lauressergues, D., Ormancey, M., Guillotin, B., San Clemente, H., Camborde, L., Duboé, C., Tourneur, S., Charpentier, P., Barozet, A., Jauneau, A., Le Ru, A., Thuleau, P., Gervais, V., Plaza, S., Combier, J.-P. (2022) Characterization of plant microRNA-encoded peptides (miPEPs) reveals molecular mechanisms from the translation to activity and specificity. Cell Rep 38, 110339
Ferré, G., Anazia, K., Silva, L.O., Thakur, N., Ray, A.P., Eddy, M.T. (2022) Global insights into the fine tuning of human A2AAR conformational dynamics in a ternary complex with an engineered G protein viewed by NMR. Cell Rep 41, 111844
Demange, P., Joly, E., Marcoux, J., Zanon, P.R.A., Listunov, D., Rullière, P., Barthes, C., Noirot, C., Izquierdo, J.-B., Rozié, A., Pradines, K., Hee, R., de Brito, M.V., Marcellin, M., Serre, R.-F., Bouchez, O., Burlet-Schiltz, O., Oliveira, M.C.F., Ballereau, S., Bernardes-Génisson, V., Maraval, V., Calsou, P., Hacker, S.M., Génisson, Y., Chauvin, R., Britton, S. (2022) SDR enzymes oxidize specific lipidic alkynylcarbinols into cytotoxic protein-reactive species. Elife11, e73913
Chadelle, L., Liu, J., Choesmel-Cadamuro, V., Karginov, A.V., Froment, C., Burlet-Schiltz, O., Gandarillas, S., Barreira, Y., Segura, C., Van Den Berghe, L., Czaplicki, G., Van Acker, N., Dalenc, F., Franchet, C., Hahn, K.M., Wang, X., Belguise, K. (2022) PKCθ-mediated serine/threonine phosphorylations of FAK govern adhesion and protrusion dynamics within the lamellipodia of migrating breast cancer cells. Cancer Lett 526, 112–130
Boudehen, Y.-M., Faucher, M., Maréchal, X., Miras, R., Rech, J., Rombouts, Y., Sénèque, O., Wallat, M., Demange, P., Bouet, J.-Y., Saurel, O., Catty, P., Gutierrez, C., Neyrolles, O. (2022) Mycobacterial resistance to zinc poisoning requires assembly of P-ATPase-containing membrane metal efflux platforms. Nat Commun 13, 4731
Atkinson, R.A. (2022) NMR of proteins and nucleic acids. Nucl Magn Reson 48, 249-270
2021
Young, J.D., Ma, M.T., Eykyn, T.R., Atkinson, R.A., Abbate, V., Cilibrizzi, A., Hider, R.C., Blower, P.J. (2021) Dipeptide inhibitors of the prostate specific membrane antigen (PSMA): a comparison of urea and thiourea derivatives. Bioorganic Med Chem Lett 128044
Schahl, A., Gerber, I.C., Réat, V., Jolibois, F. (2021) Diversity of the hydrogen bond network and its impact on NMR parameters of pmylose B polymorph: a study using molecular dynamics and DFT calculations within periodic boundary conditions. J Phys Chem B 125, 158–168
Javaid, S., Zafar, H., Atia-Tul-Wahab, Gervais, V., Ramos, P., Muller, I., Milon, A., Atta-Ur-Rahman, Choudhary, M.I. (2021) Identification of new lead molecules against anticancer drug target TFIIH subunit P8 using biophysical and molecular docking studies. Bioorg Chem 114, 105021
Hungnes, I.N., Al-Salemee, F., Gawne, P.J., Eykyn, T., Atkinson, R.A., Terry, S.Y.A., Clarke, F., Blower, P.J., Pringle, P.G., Ma, M.T. (2021) One-step, kit-based radiopharmaceuticals for molecular SPECT imaging: a versatile diphosphine chelator for 99mTc radiolabelling of peptides. Dalton Trans 50, 16156–16165
Baybekov, S., Marcou, G., Ramos, P., Saurel, O., Galzi, J.-L., Varnek, A. (2021) DMSO solubility assessment for fragment-based screening. Molecules 26, 3950
Atkinson, R.A. (2021) NMR of proteins and nucleic acids. Nucl Magn Reson 47, 204-239
2020
Schahl, A., Réat, V., Jolibois, F. (2020) Structures and NMR spectra of short amylose-lipid complexes. Insight using molecular dynamics and DFT quantum chemical calculations. Carbohydr Polym 235, 115846
Paganin-Gioanni, A., Rols, M.-P., Teissié, J., Golzio, M. (2020) Cyclin B1 knockdown mediated by clinically approved pulsed electric fields siRNA delivery induces tumor regression in murine melanoma. Int J Pharm 573, 118732
Nguyen, M.C., Saurel, O., Carivenc, C., Gavalda, S., Saitta, S., Tran, M.P., Milon, A., Chalut, C., Guilhot, C., Mourey, L., Pedelacq, J.-D. (2020) Conformational flexibility of coenzyme A and its impact on the post-translational modification of acyl carrier proteins by 4’-phosphopantetheinyl transferases. FEBS J 287, 4729–4746
Meilhoc, E., Teissie, J. (2020) Electrotransformation of Saccharomyces cerevisiae. Methods Mol Biol 2050, 187–193
Martinez, X., Chavent, M., Baaden, M. (2020) Visualizing protein structures – tools and trends. Biochem Soc Trans48, 499–506
Fontaine, C., Buscato, M., Vinel, A., Giton, F., Raymond-Letron, I., Kim, S.H., Katzenellenbogen, B.S., Katzenellenbogen, J.A., Gourdy, P., Milon, A., Flouriot, G., Ohlsson, C., Lenfant, F., Arnal, J.-F. (2020) The tissue-specific effects of different 17β-estradiol doses reveal the key sensitizing role of AF1 domain in ERα activity. Mol Cell Endocrinol 505, 110741
Del Toro, D., Carrasquero-Ordaz, M.A., Chu, A., Ruff, T., Shahin, M., Jackson, V.A., Chavent, M., Berbeira-Santana, M., Seyit-Bremer, G., Brignani, S., Kaufmann, R., Lowe, E., Klein, R., Seiradake, E. (2020) Structural basis of teneurin-latrophilin interaction in repulsive guidance of migrating neurons. Cell 180, 323-339.e19
Dekoninck, K., Létoquart, J., Laguri, C., Demange, P., Bevernaegie, R., Simorre, J.-P., Dehu, O., Iorga, B.I., Elias, B., Cho, S.-H., Collet, J.-F. (2020) Defining the function of OmpA in the Rcs stress response. Elife 9
Augenstreich, J., Haanappel, E., Sayes, F., Simeone, R., Guillet, V., Mazeres, S., Chalut, C., Mourey, L., Brosch, R., Guilhot, C., Astarie-Dequeker, C. (2020) Phthiocerol dimycocerosates from Mycobacterium tuberculosis increase the membrane activity of bacterial effectors and host receptors. Front Cell Infect Microbiol 10, 420
Atkinson, R.A. (2020) NMR of proteins and nucleic acids. Nucl Magn Reson 46, 250-271
2019
Pasquet, L., Chabot, S., Bellard, E., Rols, M.-P., Teissie, J., Golzio, M. (2019) Noninvasive gene electrotransfer in skin.Hum Gene Ther Methods 30, 17–22
Pasquet, L., Bellard, E., Chabot, S., Markelc, B., Rols, M.-P., Teissie, J., Golzio, M. (2019) Pre-clinical investigation of the synergy effect of interleukin-12 gene-electro-transfer during partially irreversible electropermeabilization against melanoma. J Immunother Cancer 7, 161
Martinez, X., Krone, M., Alharbi, N., Rose, A.S., Laramee, R.S., O’Donoghue, S., Baaden, M., Chavent, M. (2019) Molecular graphics: bridging structural biologists and computer scientists. Structure 27, 1617–1623
Ladurantie, C., Coustets, M., Czaplicki, G., Demange, P., Mazères, S., Dauvillier, S., Teissié, J., Rols, M.-P., Milon, A., Ecochard, V., Gross, G., Paquereau, L. (2019) A protein nanocontainer targeting epithelial cancers: rational engineering, biochemical characterization, drug loading and cell delivery. Nanoscale 11, 3248–3260
Kotras, C., Fossépré, M., Roger, M., Gervais, V., Richeter, S., Gerbier, P., Ulrich, S., Surin, M., Clément, S. (2019) A cationic tetraphenylethene as a light-up supramolecular probe for DNA G-quadruplexes. Front Chem 7, 493
Hedger, G., Koldsø, H., Chavent, M., Siebold, C., Rohatgi, R., Sansom, M.S.P. (2019) Cholesterol interaction sites on the transmembrane domain of the hedgehog signal transducer and class F G protein-coupled receptor smoothened. Structure 27, 549-559.e2
Guillet, V., Bordes, P., Bon, C., Marcoux, J., Gervais, V., Sala, A.J., Dos Reis, S., Slama, N., Mares-Mejía, I., Cirinesi, A.-M., Maveyraud, L., Genevaux, P., Mourey, L. (2019) Structural insights into chaperone addiction of toxin-antitoxin systems. Nat Commun 10, 782
Galant, L., Delverdier, M., Lucas, M.-N., Raymond-Letron, I., Teissie, J., Tamzali, Y. (2019) Calcium electroporation: The bioelectrochemical treatment of spontaneous equine skin tumors results in a local necrosis. Bioelectrochemistry 129, 251–258
Ferré, G., Louet, M., Saurel, O., Delort, B., Czaplicki, G., M’Kadmi, C., Damian, M., Renault, P., Cantel, S., Gavara, L., Demange, P., Marie, J., Fehrentz, J.-A., Floquet, N., Milon, A., Banères, J.-L. (2019) Structure and dynamics of G protein-coupled receptor-bound ghrelin reveal the critical role of the octanoyl chain. Proc Natl Acad Sci USA 116, 17525–17530
Ferré, G., Czaplicki, G., Demange, P., Milon, A. (2019) Structure and dynamics of dynorphin peptide and its receptor. Vitam Horm 111, 17–47
Chabot, S., Bellard, E., Reynes, J.P., Tiraby, G., Teissie, J., Golzio, M. (2019) Electrotransfer of CpG free plasmids enhances gene expression in skin. Bioelectrochemistry 130, 107343
Augenstreich, J., Haanappel, E., Ferré, G., Czaplicki, G., Jolibois, F., Destainville, N., Guilhot, C., Milon, A., Astarie-Dequeker, C., Chavent, M. (2019) The conical shape of DIM lipids promotes Mycobacterium tuberculosis infection of macrophages. Proc Natl Acad Sci USA 116, 25649–25658
Abraham, M., Apostolov, R., Barnoud, J., Bauer, P., Blau, C., Bonvin, A.M.J.J., Chavent, M., Chodera, J., Čondić-Jurkić, K., Delemotte, L., Grubmüller, H., Howard, R.J., Jordan, E.J., Lindahl, E., Ollila, O.H.S., Selent, J., Smith, D.G.A., Stansfeld, P.J., Tiemann, J.K.S., Trellet, M., Woods, C., Zhmurov, A. (2019) Sharing data from molecular simulations. J Chem Inf Model 59, 4093–4099
2018
Menchon, G., Maveyraud, L., Czaplicki, G. (2018) Molecular dynamics as a tool for virtual ligand screening. Methods Mol Biol 1762, 145–178
Gervais, V., Muller, I., Mari, P.-O., Mourcet, A., Movellan, K.T., Ramos, P., Marcoux, J., Guillet, V., Javaid, S., Burlet-Schiltz, O., Czaplicki, G., Milon, A., Giglia-Mari, G. (2018) Small molecule-based targeting of TTD-A dimerization to control TFIIH transcriptional activity represents a potential strategy for anticancer therapy. J Biol Chem 293, 14974–14988
Drożdż, W., Walczak, A., Bessin, Y., Gervais, V., Cao, X.-Y., Lehn, J.-M., Ulrich, S., Stefankiewicz, A.R. (2018) Multivalent metallosupramolecular assemblies as effective DNA binding agents. Chemistry 24, 10802–10811
Drożdż, W., Bessin, Y., Gervais, V., Cao, X.-Y., Lehn, J.-M., Stefankiewicz, A.R., Ulrich, S. (2018) Switching multivalent DNA complexation using metal-controlled cationic supramolecular self-assemblies. Chemistry 24, 1518–1521
Chavent, M., Karia, D., Kalli, A.C., Domański, J., Duncan, A.L., Hedger, G., Stansfeld, P.J., Seiradake, E., Jones, E.Y., Sansom, M.S.P. (2018) Interactions of the EphA2 kinase domain with PIPs in membranes: implications for receptor function. Structure 26, 1025-1034.e2
Chavent, M., Duncan, A.L., Rassam, P., Birkholz, O., Hélie, J., Reddy, T., Beliaev, D., Hambly, B., Piehler, J., Kleanthous, C., Sansom, M.S.P. (2018) How nanoscale protein interactions determine the mesoscale dynamic organisation of bacterial outer membrane proteins. Nat Commun 9, 2846
2017
Saurel, O., Iordanov, I., Nars, G., Demange, P., Le Marchand, T., Andreas, L.B., Pintacuda, G., Milon, A. (2017) Local and global dynamics in Klebsiella pneumoniae outer membrane protein a in lipid bilayers probed at atomic resolution. J Am Chem Soc 139, 1590–1597
Duncan, A.L., Reddy, T., Koldsø, H., Hélie, J., Fowler, P.W., Chavent, M., Sansom, M.S.P. (2017) Protein crowding and lipid complexity influence the nanoscale dynamic organization of ion channels in cell membranes. Sci Rep 7, 16647
Cukier, C.D., Tourdes, A., El-Mazouni, D., Guillet, V., Nomme, J., Mourey, L., Milon, A., Merdes, A., Gervais, V. (2017) NMR secondary structure and interactions of recombinant human MOZART1 protein, a component of the gamma-tubulin complex. Protein Sci 26, 2240–2248
Carel, C., Marcoux, J., Réat, V., Parra, J., Latgé, G., Laval, F., Demange, P., Burlet-Schiltz, O., Milon, A., Daffé, M., Tropis, M.G., Renault, M.A.M. (2017) Identification of specific posttranslational O-mycoloylations mediating protein targeting to the mycomembrane. Proc Natl Acad Sci USA 114, 4231–4236
2016
Menchon, G., Bombarde, O., Trivedi, M., Négrel, A., Inard, C., Giudetti, B., Baltas, M., Milon, A., Modesti, M., Czaplicki, G., Calsou, P. (2016) Structure-based virtual ligand screening on the XRCC4/DNA ligase IV interface. Sci Rep 6, 22878
Hemmann, J.L., Saurel, O., Ochsner, A.M., Stodden, B.K., Kiefer, P., Milon, A., Vorholt, J.A. (2016) The one-carbon carrier methylofuran from Methylobacterium extorquens AM1 contains a large number of α- and γ-linked glutamic acid residues. J Biol Chem 291, 9042–9051
Cukier, C.D., Maveyraud, L., Saurel, O., Guillet, V., Milon, A., Gervais, V. (2016) The C-terminal region of the transcriptional regulator THAP11 forms a parallel coiled-coil domain involved in protein dimerization. J Struct Biol194, 337–346
Brison, Y., Malbert, Y., Czaplicki, G., Mourey, L., Remaud-Simeon, M., Tranier, S. (2016) Structural insights into the carbohydrate binding ability of an α-(1→2) branching sucrase from glycoside hydrolase family 70. J Biol Chem 291, 7527–7540
Former lab members have moved to fresh woods, and pastures new
- Matthieu Chavent | CNRS Researcher, IPBS, Toulouse
- Adrien Schahl | Postdoctoral fellow, IPBS, Toulouse
- Virginie Gervais | CNRS Researcher I2BC, Saclay
- Guillaume Ferré | Lecturer, Université de Toulouse III – Paul Sabatier
- Nicolas Richet
- Marie Renault | Lecturer, Université de Toulouse III – Paul Sabatier
- Clément Carel | Masseur physiotherapist, Saint Orens de Gameville
- Guillaume Nars Doctor (endocrinology), CHU Strasbourg
- Parthasarathi Rath | Postdoctoral fellow, Biozentrum Basel, Switzerland
- Iordan Iordanov | Research associate, Semmelweis University, Budapest, Hungary
- Deborah Gater | Lecturer University, College London, United Kingdom
- Hélène Eury | Academic coordinator, Supexam, Rennes
- Olivier Cala | CNRS Research engineer, CRMN, Université de Lyon
- Léa Rougier | Teacher, College Elie Faure, Ste Foy La Grande
- Bruno Vincent | CNRS Engineer, Université de Strasbourg
- Corinne Hazan | General secretary, Artificial and Natural Intelligence Toulouse Institute
- Louic Vermeer | Data scientist, PGGM, Zeist, Netherlands
- Damien Bessiere | CNRS SAP engineer Toulouse
- Sébastien Campagne | INSERM Researcher, IECB, Bordeaux
- Masae Sugawara | Director of Paris Office Japan Science and Technology Agency, Paris
- Olivier Soubias | NIH Staff scientist, Bethesda, MD, USA