Explore the words cloud of the PentaBrain project. It provides you a very rough idea of what is the project "PentaBrain" about.
The following table provides information about the project.
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
|Coordinator Country||France [FR]|
|Total cost||1˙500˙000 €|
|EC max contribution||1˙500˙000 € (100%)|
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
|Duration (year-month-day)||from 2015-06-01 to 2020-05-31|
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|1||CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS||FR (PARIS)||coordinator||1˙500˙000.00|
In the brain, Cys-loop receptors mediate fast neurotransmission. They function as allosteric signal transducers across the plasma membrane: upon binding of one or more neurotransmitter molecules to an extracellular site, the receptors undergo complex conformational transitions that result in transient opening of an intrinsic ion channel. The Cys-loop family comprises receptors activated by serotonin, acetylcholine, glycine and GABA. Mammalian receptors are also the targets of a legion of psycho-active and therapeutic compounds (including nicotine, benzodiazepines, anti-emetics, general anaesthetics). Our structural knowledge is currently limited to invertebrate homologues. Atomic structures mammalian receptors are therefore acutely missing in order to understand their physiological role in molecular terms, and to be able to develop new drugs targeting them.
The project proposes to decipher the operation mechanism, the pharmacology and conformational transitions of mammalian Cys-loop receptors. Starting with a solid body of preliminary results, we will obtain new high-resolution structures, taking advantage of antibody-based crystallization chaperones. We will try and record for the first time a ‘molecular movie’ of the gating conformational transition in cristallo. On the way, we will also investigate the potential of antibody-based modulators of Cys-loop receptors for biomedical applications.
The applicant has solved in the past the structures of a bacterial Cys-loop receptor and of the mouse serotonin receptor. The proposed research will take place at the CNRS in Grenoble, France, in a very favourable environment for structural biology.
|year||authors and title||journal||last update|
Lucie Polovinkin, GheÌrici Hassaine, Jonathan Perot, Emmanuelle Neumann, Anders A. Jensen, SolÃ¨ne N. Lefebvre, Pierre-Jean Corringer, Jacques Neyton, Christophe Chipot, Francois Dehez, Guy Schoehn, Hugues Nury
Conformational transitions of the serotonin 5-HT3 receptor
published pages: 275-279, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0672-3
GhÃ©rici HassaÃ¯ne, CÃ©dric Deluz, Luigino Grasso, Romain Wyss, Ruud Hovius, Henning Stahlberg, Takashi Tomizaki, Aline Desmyter, Christophe Moreau, Lucie Peclinovska, Sonja Minniberger, Lamia Mebarki, Xiao-Dan Li, Horst Vogel, Hugues Nury
Expression, Biochemistry, and Stabilization with Camel Antibodies of Membrane Proteins: Case Study of the Mouse 5-HT3 Receptor
published pages: 139-168, ISSN: , DOI: 10.1007/978-1-4939-7151-0_8
|Methods in Molecular Biology, Membrane Protein Structure and Function Characterization||2019-05-29|
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