@article {109411,
	title = {A Gating Mechanism of Pentameric Ligand-​gated Ion Channels},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {110},
	year = {2013},
	pages = {E3987-E3996},
	abstract = {Pentameric ligand-​gated ion channels (pLGICs) play a central role in intercellular communication in the nervous system and are involved in fundamental processes such as attention, learning, and memory.  They are oligomeric protein assemblies that convert a chem. signal into an ion flux through the postsynaptic membrane, but the mol. mechanism of gating ions has remained elusive.  Here, we present atomistic mol. dynamics simulations of the prokaryotic channels from Gloeobacter violaceus (GLIC) and Erwinia chrysanthemi (ELIC)​, whose crystal structures are thought to represent the active and the resting states of pLGICs, resp., and of the eukaryotic glutamate-​gated chloride channel from Caenorhabditis elegans (GluCI)​, whose openchannel structure was detd. complexed with the pos. allosteric modulator ivermectin.  Structural observables extd. from the trajectories of GLIC and ELIC are used as progress variables to analyze the time evolution of GluCI, which was simulated in the absence of ivermectin starting from the structure with bound ivermectin.  The trajectory of GluCI with ivermectin removed shows a sequence of structural events that couple agonist unbinding from the extracellular domain to ion-​pore closing in the transmembrane domain.  Based on these results, we propose a structural mechanism for the allosteric communication leading to deactivation​/activation of the GluCI channel.  This model of gating emphasizes the coupling between the quaternary twisting and the opening​/closing of the ion pore and is likely to apply to other members of the pLGIC family.},
	author = {Nicolas Calimet and Manuel Simoes and Jean-Pierre Changeux and Martin Karplus and Antoine Taly and Marco Cecchini}
}
