|Nuclear Magnetic Resonance of Biomolecules - CNRS URA 2185|
|HEAD||DELEPIERRE Muriel / firstname.lastname@example.org|
|MEMBERS||DR Amorim de Cardoso Gisèle, Babault Nicolas, Caillet-Saguy Célia, Dr Chaffotte Alain, Dr Cordier Florence, Dr Guijarro Inaki, Guillière Florence, Dr Izadi-Pruneyre Nadia, Dr Lecroisey Anne, Dr Prochnicka-Chalufour Ada, Simenel Catherine, Terrien Elouan, Theilllet François-Xavier, Dr Wecker Karine, Dr Wolff Nicolas
Our research area is mainly dedicated to the structure determination of proteins, peptides, nucleic acids and oligosaccharides, in relation to their function but also to molecular interactions studies. The driving force is to adapt NMR techniques to biological problems. How can NMR be used to answer a peculiar question and is NMR the only tool to answer it? Thus, not only modern NMR techniques are employed but also different biophysical approaches are used.
Structural and functional studies of bacterial proteins involved in heme acquisition
Several pathogenic gram-negative bacteria use a heme uptake system involving an extracellular heme-binding protein called hemophore that acquires free or hemoprotein-bound heme and transfers it to its specific outer membrane receptor, via protein-protein interaction. Over the years we have been involved in the molecular characterization of all steps of the mechanism at both structural and functional levels, from hemophore secretion, to heme delivery to the cell via heme uptake and release to the receptor. Particularly hemophore’s structures in holo and apo forms have been solved and interaction with its receptor characterized.
Structural studies of antigenic determinants recognized by a protective monoclonal antibody in view of developing a vaccine against shigellosis
A possible strategy for human vaccination against shigellosis is to develop synthetic chemically defined vaccines with simple molecules able to mimic the O-SP that would induce the synthesis of protective antibodies. The conformations and the epitopes of oligosaccharides from O-SP of two different serotypes, 5a and 2a, free and bound to protective monoclonal have been characterized.
Structure, function of transcription regulators from hyperthermophile-Archaea viruses
Hyperthermophile-archaea viruses show an exceptional diversity and are very different from viruses that infect bacteria and eukaryotes. Study of the structure and function of proteins that could be involved in transcription regulation, a phenomena essential for infection, has been initiated. The first protein studied, D56, belongs to the virus Sulfolobus islandicus rudivirus (SIRV1) and is expressed throughout the infection cycle of the virus. It interacts specifically with the regions of its own promoter and of the promoter of a neighboring gene. The protein forms a dimer and its structure has been solved whereas its interaction with DNA sequences from its promoter has been characterized. The second protein, Sta1, is a host protein that activates transcription of SIRV1 genes. A model of its structure has been established and validated using NMR.
Structural and functional studies of NEMO, a regulatory protein of the NF-κB pathway
NEMO is a central regulatory protein of the NF-κB signaling pathway, notably involved in early inflammatory and immune responses and in regulation of apoptosis as well as oncogenesis. In order to understand the molecular mechanism by which NEMO participates in NF-κB activation and to facilitate the elaboration of anti-inflammatory and anti-cancer drugs, we are studying the biophysical, structural and functional characteristics of the C-terminal regulatory domains of NEMO and their interactions with biological partners and with small inhibitory molecules.
Structural study of proteins involved in the late transcription program in the forespore
Sporulation is a primitive developmental process carried out by Bacilli and Clostridia in response to nutrient starvation, involving the formation of a forespore and a mother cell. Each cell implements an early and a late transcription program under the control of proteins associated with RNA polymerase, the sigma factors. The late forespore sigma factor (sigma-G) is maintained in an inactive form by a recently identified inhibitor (Gin) and its activity is released after complete engulfment of the forespore by the mother cell. To understand the mechanism by which Gin inhibits sigma-G at a specific developmental stage, we are studying the biophysical and structural properties of Gin and its interaction with sigma-G.
WOLFF, N., IZADI-PRUNEYRE, N., COUPRIE, J., HABECK, M., LINGE, J., RIEPING, W., WANDERSMAN, C., NILGES, M., DELEPIERRE, M., LECROISEY, A. (2008) Comparative Analysis of Structural and Dynamics Properties of the Loaded and Unloaded Hemophore HasA: Functional Implications.Journal of Molecular Biology 376, 517-525.PMID 18 164722
CORDIER, F., VINOLO, E., VERON, M., DELEPIERRE, M., AGOU, F. (2008) Solution Structure of NEMO wild type and pathogenic C147F mutant zinc-finger – structural and functionnal incidence on NF-KB activation.Journal of Molecular Biology377, 1419-1432.PMID 18 313693
CAILLET-SAGUY, C., TURANO, P., PICCIOLI, M., LUKAT-RODGERS, G.S., CZJEK, M., GUIGLIARELLI, B., IZADI-PRUNEYRE, N., ROGERS, K.R., DELEPIERRE, M., LECROISEY, A. (2008) Deciphering the Structural role of Hisitidine 83 for Heme binding in Hemophore HasA.Journal of Biological Chemistry283, 5960-5970.PMID 18 162469
LEFEVRE, J., DELEPELAIRE, P., DELEPIERRE, M., IZADI-PRUNEYRE, N. (2008) Modulation by substrates of the interaction between the HasR outer membrane receptor and its specific TonB-like protein, HasB.Journal of Molecular Biology378, 840-8. PMID 18 402979
KESSLER, A., SEZONOV, G., GUIJARRO, J.I., DESNOUES, N., ROSE, T., DELEPIERRE,M., BELL, S., PRANGISHVILI, D. (2006) A novel archaeal regulatory protein, Sta1, activates transcription from viral promoters. Nucleic Acid Research34, 4837-4845.PMID 16 973899
Activity Reports 2009 - Institut Pasteur
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