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PentaBrain SIGNED

Structural studies of mammalian Cys-loop receptors

Total Cost €

0

EC-Contrib. €

0

Partnership

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 PentaBrain project word cloud

Explore the words cloud of the PentaBrain project. It provides you a very rough idea of what is the project "PentaBrain" about.

cristallo    environment    function    neurotransmitter    extracellular    understand    starting    conformational    cnrs    intrinsic    family    mammalian    proposes    movie    membrane    structures    advantage    fast    benzodiazepines    mechanism    grenoble    modulators    obtain    compounds    acutely    opening    bacterial    anti    solved    undergo    activated    limited    first    invertebrate    solid    preliminary    brain    psycho    transducers    signal    gating    missing    receptors    mediate    site    atomic    glycine    plasma    binding    anaesthetics    nicotine    transient    cys    mouse    ion    receptor    allosteric    body    neurotransmission    gaba    emetics    structural    homologues    channel    record    antibody    pharmacology    biomedical    loop    crystallization    acetylcholine    operation    time    resolution    molecules    serotonin    transition    active    biology    drugs    transitions    place    physiological    therapeutic    france    molecular    legion    chaperones    decipher   

Project "PentaBrain" data sheet

The following table provides information about the project.

Coordinator
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS 

Organization address
address: RUE MICHEL ANGE 3
city: PARIS
postcode: 75794
website: www.cnrs.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-06-01   to  2020-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS FR (PARIS) coordinator 1˙500˙000.00

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 Project objective

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.

 Publications

year authors and title journal last update
List of publications.
2018 Lucie Polovinkin, Ghérici Hassaine, Jonathan Perot, Emmanuelle Neumann, Anders A. Jensen, Solène 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
Nature 563/7730 2020-02-06
2017 Ghérici Hassaïne, Cédric 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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