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© Marie Prévost, Institut Pasteur
Image of a portion of a Xenopus oocyte expressing a channel receptor.
Publication : eLife

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in eLife - 15 Mar 2017

Menny A, Lefebvre SN, Schmidpeter PA, Drège E, Fourati Z, Delarue M, Edelstein SJ, Nimigean CM, Joseph D, Corringer PJ

Link to Pubmed [PMID] – 28294942

Elife 2017 03;6

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.

https://www.ncbi.nlm.nih.gov/pubmed/28294942