Fig. 6.
Two stabilization networks are used in GLIC to maintain the channel open. (A) View of the GLIC wild-type open-form structure. Two adjacent subunits are highlighted. (B) Multiple-sequence alignment of GLIC and its homologs in a limited set of regions to highlight the positions in GLIC (colored in red) whose mutation traps GLIC in LC conformation. The alignment contains GLIC (G. violaceus) and ELIC (E. chrysanthemi), sTeLIC (symbiont of the worm Tevnia), GluCl (a glutamate-gated chloride ion channel from Caenorhabditis elegans), α1-GlyR (the glycine receptor α1 subunit from zebrafish), and 5HT3A (the serotonin receptor from mouse). The remaining sequences are representatives for human pLGICs. Numbering refers to the GLIC protein sequence. The yellow stars indicate the residues forming the primary electrostatic triad and the purple stars indicate residues involved in the secondary electrostatic triad. The TGW motif in GLIC is boxed. (C and D) Two branches of a continuous network originating from E35 that reach, independently, the middle transmembrane region (H235) of two adjacent subunits. The proton-sensor E35 and key residues responsible for channel activation are shown as sticks. (C) View from outside the pentamer with the first network shown as a purple line, across subunits. (D) View from inside the pentamer showing the second network involving the hydrophobic cluster as an orange line, within the same subunit.