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Pentameric ligand-gated ion channels gating mechanism using a bacterial prototype

Doctor Pierre-Jean Corringer (Laboratoire Récepteurs-canaux, Institut Pasteur, Paris, France), will give a lecture about "Pentameric ligand-gated ion channels gating mechanism using a bacterial prototype", the 16th november 2018.
Ajouter à mon agenda 2024-03-29 14:30:38 2024-03-29 14:30:38 Pentameric ligand-gated ion channels gating mechanism using a bacterial prototype Doctor Pierre-Jean Corringer (Laboratoire Récepteurs-canaux, Institut Pasteur, Paris, France), will give a lecture about "Pentameric ligand-gated ion channels gating mechanism using a bacterial prototype", the 16th november 2018. D'Alembert building, Fonteneau amphitheater ENS-PARIS-SACLAY webmaster@ens-paris-saclay.fr Europe/Paris public

Pentameric channel-receptors, including nicotinic acetylcholine, glycine and GABAA 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, helped solving its X-ray structure in two closed and one open conformation.

Protein dynamics

To investigate the dynamics of the protein, we further engineered multiple fluorescent/quencher pairs that report on the protein conformation. Our data show that, upon activation by protons, the protein first undergoes a rapid (faster than a ms) and global pre-activation transition, followed by a more local channel opening. Mapping of the titrable residues also identify the key protein domains mediating proton activation.

These data collected on a model pLGIC help understanding the mechanism of functioning of neurotransmitter-gated channel for which intermediate conformation also contribute the activation transition pathway.

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