Thompson AJ , Alqazzaz M , Ulens C , Lummis SC .

Wellcome Trust

	Fig. 1. An alignment of channel-lining residues for a range of eukaryotic Cys-loop receptors and prokaryotic homologues. As is common for these receptors, a prime notation is used to facilitate comparison between different subunits, with 0′ being the conserved charged residue at the start of M2. Grey indicates residue conservation. Accession numbers are: ELIC P0C7B7, GLIC Q7NDN8, 5-HT3P46098, nACh α1 P02708, Gly P23415, GABAA α1 P14867, GABAA β2 P47870, GABAA γ2 P18507, GluCl Q94900.
	Fig. 2. GABA and 5-AV agonist concentration–response curves (A) and example responses (B). The black bar is the application of agonist. Data = mean ± SEM, n ≥ 4.
	Fig. 3. ELIC antagonists. (A) Example traces showing inhibition by picrotoxinin (PXN). Concentration–inhibition curves for PXN (B), α-endosulfan (C), and rimantadine (D). Inhibition was measured at the GABA EC50 (1.6 mM). Data = mean ± SEM, n ≥ 4. Values derived from the curves can be found in Table 2.
	Fig. 4. (A) An overlay of all 10 docked poses for α-endosulfan. The channel volume occupied by 10 poses are calculated from the Van der Waals radii and are shown in wireframe. Inset Structure of α-endosulfan. Scale = 2.5 Å. (B) A single pose showing the channel from the side. There are hydrogen bond interactions with 6′ Thr residues from adjacent subunits. (C) The same pose is seen from above, looking down towards the cell intererior. (D) Concentration response curves show Q2′N and T6'S mutations caused a decrease in α-endosulfan potency.
	Fig. 5. Comparison of pIC50 values from ELIC with those previously reported at GLIC (Alqazzaz et al., 2011). Compounds are almost all less potent at ELIC and fewer compounds inhibit responses.

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