Identification of a pre-active conformation of a pentameric channel receptor. Academic Article uri icon

Overview

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.

publication date

  • March 15, 2017

Research

keywords

  • Bacterial Proteins
  • Bridged Bicyclo Compounds, Heterocyclic
  • Cyanobacteria
  • Ligand-Gated Ion Channels

Identity

PubMed Central ID

  • PMC5398890

Scopus Document Identifier

  • 85018481180

Digital Object Identifier (DOI)

  • 10.1038/nchembio801

PubMed ID

  • 28294942

Additional Document Info

volume

  • 6