Identification of a pre-active conformation of a pentameric channel receptor - Sorbonne Université
Journal Articles eLife Year : 2017

Identification of a pre-active conformation of a pentameric channel receptor

Abstract

Pentameric ligand-gated ion channels (pLGICs) mediate fast chemical signaling through global allosteric transitions. Despite the existence of several high-resolution structures of pLGICs, their dynamical properties remain elusive. Using the proton-gated channel GLIC, we engineered multiple fluorescent reporters, each incorporating a bimane and a tryptophan/tyrosine, whose close distance causes fluorescence quenching. We show that proton application causes a global compaction of the extracellular subunit interface, coupled to an outward motion of the M2-M3 loop near the channel gate. These movements are highly similar in lipid vesicles and detergent micelles. These reorganizations are essentially completed within 2 ms and occur without channel opening at low proton concentration, indicating that they report a pre-active intermediate state in the transition pathway toward activation. This provides a template to investigate the gating of eukaryotic neurotransmitter receptors, for which intermediate states also participate in activation.
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hal-01519856 , version 1 (09-05-2017)

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Anaïs Menny, Solène N Lefebvre, Philipp Am Schmidpeter, Emmanuelle Drège, Zaineb Fourati, et al.. Identification of a pre-active conformation of a pentameric channel receptor. eLife, 2017, 6, pp.e23955. ⟨10.7554/eLife.23955⟩. ⟨hal-01519856⟩
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