Full mutational mapping of titratable residues helps to identify proton-sensors involved in the control of channel gating in the Gloeobacter violaceus pentameric ligand-gated ion channel

• DOI: 10.1371/journal.pbio.2004470
• Publication Date: 2017-12-27T13:25:56Z
• Authors: Ákos Nemecz; Haidai Hu; Zaineb Fourati; Catherine Van Ren...; Marc Delarue; Pierre-Jean Corri...
• Keywords: Models, Molecular; 0303 health sciences; QH301-705.5; [SCCO.NEUR]Cognitive science/Neuroscience; Ligand-Gated Ion Channels; Cyanobacteria; Ligands; [SCCO]Cognitive science; 03 medical and health sciences; Bacterial Proteins; Mutagenesis, Site-Directed; Biology (General); Protons; Ion Channel Gating; Research Article; Signal Transduction

The Gloeobacter violaceus ligand-gated ion channel (GLIC) has been extensively studied by X-ray crystallography and other biophysical techniques. This provided key insights into the general gating mechanism of pentameric (pLGIC) signal transduction. However, GLIC is activated lowering pH location its putative proton activation site(s) still remain(s) unknown. To this end, every Asp, Glu, His residue was mutated individually or in combination investigated electrophysiology. In addition to mutational analysis, mutations were structurally resolved address whether particular residues contribute sensing, alternatively GLIC-gating, independently side chain protonation. data show that multiple located below orthosteric site, notably E26, D32, E35, D122 lower part extracellular domain (ECD), along with E222, H235, E243, H277 transmembrane (TMD), alter activation. H235 found also expression. E35 identified as a proton-sensing residue, whereby neutralization carboxylate stabilizes active state. Thus, occurs allosterically at level loci contribution coupling interface between ECD TMD.