Mardi 11 novembre 2014 à 10h30, dans le grand amphithéâtre de l'IPT, Pierre-Jean Corringer,

Directeur de Recherche CNRS, Chef du laboratoire "Récepteurs-canaux" à l'Institut Pasteur, Paris, proposera une conférence intitulée "Structure et modulation allostérique des récepteurs nicotiniques de l'acetylcholine et de leur homologue".

Résumé de la conférence :
Pentameric channel-receptors, including nicotinic acetylcholine and GABA_A receptors, play a key role in fast excitatory and inhibitory transmission in the nervous system and are the target of numerous therapeutic and addictive drugs. They carry several neurotransmitter binding sites which govern the opening of a transmembrane ion channel. Extensively expressed in animals, they were found in several bacteria, especially the homolog from the cyanobacteria Gloeobacter violaceus (GLIC) which functions as a proton-gated ion channel. The simplified architecture of this archaic homologue, as well as its prokaryotic origin, allowed solving its X-ray structure in two closed and one open conformation. This suggests that channel opening occurs through symmetrical quaternary twist and “blooming” motions, together with tertiary deformation, according to a global transition that couples channel opening with reorganization of the binding pockets for neurotransmitters and allosteric effectors. In addition, co-crystallization of GLIC with allosteric inhibitors that are clinically used as general anesthetics reveals the mechanism of action at the membrane of these amphipatic molecules and will help designing new drugs targeted to pentameric channel-receptors. Altogether, these combined structural and functional data give insights into the allosteric mechanisms operating in these integral membrane proteins.