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Structural basis of nicotinic acetylcholine receptor function (NICOTINIC RECEPTORS)

Objective

We aim to determine the 3D structure of the prototypic neurotransmitter receptor, the nicotinic acetylcholinereceptor (Ache), at high resolution, for understanding the structural basis of its function, using advanced electron and X-ray crystallography, NMR, AFM, molecular modelling and electro physiology, combined with antibody and legend labelling. The best available image of a neurotransmitter receptor is that of the Ache at 4.6AA resolution, obtained by partner 2. Our objectives are to achieve:
a. high resolution structure of closed and open Ache channels by electron microscopy;
b. imaging individual Aches in action by AFM;
c. X-ray structure of Ache channels;
d. conformation (by NMR and X-ray crystallography) of Ache fragments;
e. characterization of legend and protein binding properties;
f. detailed models of Torpedo and human Aches byte combined results, rational design of subtype-specific legends and legend assessment by electro physiology. Elucidation of the structure-function relationship of Aches will be catalytic to numerous studies in synapse function and dysfunction.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

HELLENIC PASTEUR INSTITUTE
Address
127,Vassilissis Sofias Av. 127
11521 Athens
Greece

Participants (6)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
Rue Grandville 1
54001 Nancy
ELI LILLY COMPANY LIMITED
United Kingdom
Address
Erl Wood Manor
GU20 6PH Windlesham
FREIE UNIVERSITAET BERLIN
Germany
Address
Thielallee 63
14195 Berlin
MRC Laboratory of Molecular Biology
United Kingdom
Address
Hills Road
CB2 2QH Cambridge
UNIVERSITAET KONSTANZ
Germany
Address
10,Universitaetsstrasse 10
78457 Konstanz
UNIVERSITE DE BORDEAUX I
France
Address
Avenue Pey-berland 16
33607 Pessac