Eva Pebay-Peyroula Team
In March 2017, we organize a winter school entitled “Biology at different scales” see http://www.leshouches.strikingly.com
- Eva Pebay-Peyroula (Professor, Université Grenoble Alpes)
- Stéphanie Ravaud (Assistant Professor, Université Grenoble Alpes)
- Hugues Nury (Researcher, CNRS)
- Florine Dupeux (Research engineer)
- Jonathan Perot (Research engineer)
- Orso Subrini (Postdoctoral fellow)
- Aleksandra Woznicka (PhD student)
- Lucie Peclinovska (PhD student)
- Céline Juillan-Binard (Technician)
- Delphine Blot (Technician)
email adress: first-name.family-name at ibs.fr
Our group is interested in several membrane proteins: nucleotide transporters (from mitochondria, chloroplasts and intracellular bacteria), Cys-loop receptors and a phosphate transporter. We aim at understanding structure-function relationships based on structural studies, complemented with functional, biophysical and computational techniques.
In 2003, we solved the first structure of the mitochondrial ADP/ATP carrier (AAC), a MCF member (Mitochondrial carrier family). MCF carriers play a crucial role in importing and exporting in a very specific manner, the substrates or products of all metabolic reactions that occur within mitochondria. The overall structure of AAC shed light on the fold of MCF carriers. The detailed analysis of AAC opened the way to several hypotheses concerning substrate binding and transport mechanism. Activity measurements combined synergistically with molecular-dynamics simulations demonstrate how all documented pathological mutations alter the binding affinity and the translocation kinetics of the nucleotides. We could thus through a bridge between pathologies and their molecular origins. Many questions still remain open among which understanding the specificity of MCF carriers and the dynamics needed for conformational changes.
In the last years, we started to study another family of nucleotide transporters (NTTs) from chloroplasts and intracellular pathogenic bacteria. Their mechanism of action is probably different as they exchange ATP against ADP and Pi, and are predicted to bare 12 transmembrane helices. We developed production, purification and characterization protocols and are currently trying to crystallize several NTTs.
Bruno Miroux, IBPC, Paris, France
Chris Chipot, CNRS-Univ Nancy, France
Marc Le Maire, CEA Saclay, France
Contact: Stéphanie.Ravaud at ibs.fr or Eva.Pebay-Peyroula at ibs.fr
5-HT3 receptor and mammalian Cys-loop receptors
In the brain, fast neurotransmission involves the release of neurotransmitters in the synapse, their binding to specific receptors, which then open and let ions flow over the postsynaptic membrane. The Cys-loop receptor family directly mediates this neurotransmission. The 5-HT3 receptor is a serotonin-gated member of the family and possesses a channel permeable to cations. Granisetron and similar drugs are prominent antagonists of 5-HT3 receptor, and widely used as anti-emetic drugs following chemotherapy or surgery. We have recently solved a first structure of the mouse 5-HT3A receptor in complex with stabilizing llama-derived antibodies.
Horst Vogel, EPFL Lausanne, Switzerland
Ghérici Hassaine, Theranyx Marseille, France
Contact: Hugues.Nury at ibs.fr
Phosphate transporter from Toxoplasma gondii
Collaboration with Karsten Fischer, University of Tromsø, Norway
TSPO, a model protein for serial crystallography
Collaboration with Manfred Burghammer, ESRF
From left to rigth: Lucie, Guillaume, Ola, Jo, Florine, Delphine, Stéphanie, Orso, Hugues, Eva