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ICaRO SIGNED

Ion Channels and Receptors Operation

Total Cost €

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EC-Contrib. €

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Partnership

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Project "ICaRO" data sheet

The following table provides information about the project.

Coordinator
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE 

Organization address
address: RUE DE TOLBIAC 101
city: PARIS
postcode: 75654
website: www.inserm.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]
 Project website https://sites.google.com/view/fm4b-lab/group-members/dr-arin-marchesi
 Total cost 173˙076 €
 EC max contribution 173˙076 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-06-13   to  2018-06-12

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE FR (PARIS) coordinator 173˙076.00

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 Project objective

Our understanding of ion channel operation is limited to inferences based on functional data and to static snapshots of their structures where they are available. Cyclic nucleotide-modulated channels and calcium-activated K channels play crucial roles in a myriad of physiological processes ranging from signal transduction to neuronal excitability. The binding of ligands to specialized intracellular domains modulates the opening/closing (gating) equilibrium of these channels. Both the high resolution structures - in open and closed conformation - of these channels and the precise mechanism of ligand-mediated channel activation are unknown. The present proposal aims to understand the mechanism of ion channel modulation by ligands. To accomplish this goal we will utilize prokaryotic homologues of these channels reconstituted in artificial membranes. High-speed atomic force microscopy (HS-AFM) will allow us to directly observe individual ion channel molecules in action at high spatiotemporal resolution and in physiological conditions. Through UV-laser pulses caged ligands (caged-Ca2 or caged-cAMP) will be liberated during HS-AFM imaging and the conformational changes associated to ligand binding monitored in real time. Differences between liganded and unliganded channel structures will provide insight into the mechanism of ligand gating. The obtained data will be compared to single channel current recordings under comparable conditions.

 Publications

year authors and title journal last update
List of publications.
2018 Luisa M. R. Napolitano, Arin Marchesi, Alex Rodriguez, Matteo De March, Silvia Onesti, Alessandro Laio, Vincent Torre
The permeation mechanism of organic cations through a CNG mimic channel
published pages: e1006295, ISSN: 1553-7358, DOI: 10.1371/journal.pcbi.1006295
PLOS Computational Biology 14/8 2019-06-13
2018 Fidan Sumbul, Arin Marchesi, Hirohide Takahashi, Simon Scheuring, Felix Rico
High-Speed Force Spectroscopy for Single Protein Unfolding
published pages: 243-264, ISSN: , DOI: 10.1007/978-1-4939-8591-3_15
Nanoscale Imaging 2019-06-13
2018 Francesca Zuttion, Lorena Redondo-Morata, Arin Marchesi, Ignacio Casuso
High-Resolution and High-Speed Atomic Force Microscope Imaging
published pages: 181-200, ISSN: , DOI: 10.1007/978-1-4939-8591-3_11
Nanoscale Imaging 2019-06-13
2018 Fidan Sumbul, Arin Marchesi, Felix Rico
History, rare, and multiple events of mechanical unfolding of repeat proteins
published pages: 123335, ISSN: 0021-9606, DOI: 10.1063/1.5013259
The Journal of Chemical Physics 148/12 2019-06-13
2018 Arin Marchesi, Xiaolong Gao, Ricardo Adaixo, Jan Rheinberger, Henning Stahlberg, Crina Nimigean, Simon Scheuring
An iris diaphragm mechanism to gate a cyclic nucleotide-gated ion channel
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-06414-8
Nature Communications 9/1 2019-04-03

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