Accueil > Research > Research groups > Membrane Transport Group (H. Nury) > Nury & Pebay-Peyroula Team
Nury & Pebay-Peyroula teamPresentationOur research aims to better understand how membrane machines operate at the molecular scale, using structural biology. We mainly work with pentameric neurotransmitter-gated channels, and with the phosphate transporter of Toxoplasma gondii. Pentameric ligand-gated ion channels (pLGICs)In the nervous system, pLGICs mediate fast neurotransmission. They function as allosteric signal transducers across the plasma membrane : upon binding neurotransmitter molecules, they undergo complex conformational transitions that result in transient openings of an intrinsic ion channel. The family comprises receptors activated by glycine, GABA, acetylcholine and serotonin. We aim to reveal the operation mechanism(s) of pLGICs, to decipher their conformational transitions, to understand their pharmacology. We have obtained results mostly with the serotonin 5-HT3 receptor.
Collaborations : Funding APT, the Apicoplast Phosphate Transporter from T.gondii , E.Pebay-PeyroulaPlasmodium and Toxoplasma gondii are obligate intracellular parasites that harbor a plastid, the apicoplast, which is responsible for vital functions such as fatty acid synthesis and isoprenoid synthesis. The import of the essential substrates for these pathways have been shown to be relying on the sole characterized transporter of the apicoplast of T. gondii and Plasmodium : APT. APT belongs to the family of triosephosphate/phosphate transporters found in plant chloroplasts. It was shown that the disruption of the APT gene in T. gondii leads to immediate death of the parasite. Our project aims at solving the structure of APT, at atomic resolution by X-ray crystallography. Since 2015, we set-up production protocols and characterization technics (thermal stability, transport properties,...). More recently, we exploit nanobodies to stabilize single conformations and enhance the chances to get crystals. Collaborations : High throughput in meso membrane protein crystallization platform, F. DupeuxThe team includes the lipidic cubic phase crystallization platform (HTMPC). Major past achievementsBacterial rhodopsins (1994-2004), E. Pebay-Peyroula
The mitochondrial ADP/ATP carrier (2000-2017), E.Pebay-Peyroula and S.Ravaud From 2000 to 2017 we investigated the transport of nucleotides in mitochondria and also in chloroplasts and obligate intracellular bacteria. In 2003, we solved the first structure of the mitochondrial ADP/ATP carrier (AAC), a MCF member (Mitochondrial carrier family) (Pebay-Peyroula et al. Nature 2003). Theoretical calculations showed the importance of electrostatics in attracting nucleotides to their binding site (Dehez et al. JACS 2008). 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 (Ravaud et al. ACS ChemBio 2003). We also studied 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.
Ph.D. thesesA list of Ph.Ds. in the group can be found here. Key publicationsThe complete list of our publications is available here. Team membersCéline Juillan-Binard (Research technican CEA)
Alumni Work with usIf you are interested in our research, get in contact with Hugues or Eva. Applications from scientists who like their job with passion and do it with rigour, at any career stage, will be considered with care. |
First structure of a membrane protein crystallized in lipidic cubic phases
