Identification of a pre-active conformation of a pentameric channel receptor
- Institut Pasteur, France
- Weill Cornell Medicine, United States
- Université Paris-Sud, France
- Inserm U1024, CNRS 8197, Institute of Biology, Ecole Normale Supérieure, France
Abstract
Pentameric ligand-gated ion channels (pLGICs) mediate fast chemical signalling 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 towards activation. This provides a template to investigate the gating of eukaryotic neurotransmitter receptors, for which intermediate states also participate in activation.
Article and author information
Author details
Pierre-Jean Corringer
Funding
Agence Nationale de la Recherche (Pentagate)
- Anaïs Menny
- Solène N Lefebvre
- Emmanuelle Drège
- Zaineb Fourati
- Marc Delarue
- Delphine Joseph
- Pierre-Jean Corringer
Centre National de la Recherche Scientifique (UMR 3571)
- Anaïs Menny
- Solène N Lefebvre
- Delphine Joseph
Institut Pasteur
- Anaïs Menny
- Solène N Lefebvre
- Zaineb Fourati
- Marc Delarue
- Pierre-Jean Corringer
Université Pierre et Marie Curie (PhD student fellowship)
- Anaïs Menny
- Solène N Lefebvre
Fondation pour la Recherche Médicale (DEQ20140329497)
- Anaïs Menny
- Pierre-Jean Corringer
National Institutes of Health (R01 GM088352)
- Crina M Nimigean
Centre National de la Recherche Scientifique (UMR 8076)
- Emmanuelle Drège
- Delphine Joseph
Centre National de la Recherche Scientifique (UMR 3528)
- Zaineb Fourati
- Marc Delarue
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Menny et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Identification of a pre-active conformation of a pentameric channel receptor
eLife 6:e23955.
https://doi.org/10.7554/eLife.23955
