Daeffler KN , Lester HA , Dougherty DA .

NS034407 NINDS NIH HHS , R01 NS034407 NINDS NIH HHS , R37 NS034407 NINDS NIH HHS

	Figure 1. Glutamate binding site and predicted electrostatic interactions between the ligand and its surrounding amino acids. Residues from the primary face are colored in green and the complementary face in blue.
	Figure 2. Chemical structures of amino acids used in this study.
	Figure 3. Plot of cation−π binding energy vs mutant receptor loss-of-function at Y206. A linear trend is indicative of an electrostatic interaction with the face of the residue examined. Data for both the wild type and α signal peptide-containing templates are plotted together and indicate no effect of altering the signal peptide on receptor function.
	Figure 4. Predicted hydrogen bond interactions between the primary and complementary subunits near the ligand-binding site in the 3RIF crystal structure. Residues on the primary face are shown in green, residues on the complementary face in blue, and glutamate in white. Hydrogen bond network between (A) the C loop of the primary subunit and the F loop of the complementary subunit and (B) the B loop of the primary subunit and the E loop of the complementary subunit.

Aziz, Efficacy and tolerance of ivermectin in human onchocerciasis. 1982, Pubmed

Aziz, Efficacy and tolerance of ivermectin in human onchocerciasis. 1982, Pubmed
Beene, Cation-pi interactions in ligand recognition by serotonergic (5-HT3A) and nicotinic acetylcholine receptors: the anomalous binding properties of nicotine. 2002, Pubmed , Xenbase
Blum, Evidence for an extended hydrogen bond network in the binding site of the nicotinic receptor: role of the vicinal disulfide of the alpha1 subunit. 2011, Pubmed , Xenbase
Bocquet, X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation. 2009, Pubmed
Boyd, Cell surface expression of 5-hydroxytryptamine type 3 receptors is controlled by an endoplasmic reticulum retention signal. 2003, Pubmed
Brejc, Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. 2001, Pubmed
Campbell, Ivermectin: an update. 1985, Pubmed
Campbell, Ivermectin: a potent new antiparasitic agent. 1983, Pubmed
Castillo, Role of the N-terminal alpha-helix in biogenesis of alpha7 nicotinic receptors. 2009, Pubmed , Xenbase
Coe, Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. 2005, Pubmed , Xenbase
Cupp, The effects of ivermectin on transmission of Onchocerca volvulus. 1986, Pubmed
Etter, An amino acid substitution in the pore region of a glutamate-gated chloride channel enables the coupling of ligand binding to channel gating. 1996, Pubmed , Xenbase
Filatov, The role of conserved leucines in the M2 domain of the acetylcholine receptor in channel gating. 1995, Pubmed , Xenbase
Frazier, An engineered glutamate-gated chloride (GluCl) channel for sensitive, consistent neuronal silencing by ivermectin. 2013, Pubmed
Gleitsman, An intersubunit hydrogen bond in the nicotinic acetylcholine receptor that contributes to channel gating. 2008, Pubmed
Hibbs, Principles of activation and permeation in an anion-selective Cys-loop receptor. 2011, Pubmed
Hilf, X-ray structure of a prokaryotic pentameric ligand-gated ion channel. 2008, Pubmed
Hilf, Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel. 2009, Pubmed
Kao, A simple and efficient method to reduce nontemplated nucleotide addition at the 3 terminus of RNAs transcribed by T7 RNA polymerase. 1999, Pubmed
Kearney, Determinants of nicotinic receptor gating in natural and unnatural side chain structures at the M2 9' position. 1996, Pubmed , Xenbase
Kracun, Influence of the M3-M4 intracellular domain upon nicotinic acetylcholine receptor assembly, targeting and function. 2008, Pubmed
Labarca, Channel gating governed symmetrically by conserved leucine residues in the M2 domain of nicotinic receptors. 1995, Pubmed , Xenbase
Lester, Cys-loop receptors: new twists and turns. 2004, Pubmed
Lummis, A cation-pi binding interaction with a tyrosine in the binding site of the GABAC receptor. 2005, Pubmed
Marotta, Probing the non-canonical interface for agonist interaction with an α5 containing nicotinic acetylcholine receptor. 2014, Pubmed , Xenbase
Mecozzi, Cation-pi interactions in aromatics of biological and medicinal interest: electrostatic potential surfaces as a useful qualitative guide. 1996, Pubmed
Miller, Binding, activation and modulation of Cys-loop receptors. 2010, Pubmed
Miyazawa, Nicotinic acetylcholine receptor at 4.6 A resolution: transverse tunnels in the channel wall. 1999, Pubmed
Mossessova, SNARE selectivity of the COPII coat. 2003, Pubmed
Mu, Different binding orientations for the same agonist at homologous receptors: a lock and key or a simple wedge? 2003, Pubmed
Nowak, In vivo incorporation of unnatural amino acids into ion channels in Xenopus oocyte expression system. 1998, Pubmed , Xenbase
Padgett, Unnatural amino acid mutagenesis of the GABA(A) receptor binding site residues reveals a novel cation-pi interaction between GABA and beta 2Tyr97. 2007, Pubmed , Xenbase
Placzek, An alpha7 nicotinic acetylcholine receptor gain-of-function mutant that retains pharmacological fidelity. 2005, Pubmed , Xenbase
Pless, A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue. 2008, Pubmed , Xenbase
Pons, Critical role of the C-terminal segment in the maturation and export to the cell surface of the homopentameric alpha 7-5HT3A receptor. 2004, Pubmed
Puskar, Two neuronal nicotinic acetylcholine receptors, alpha4beta4 and alpha7, show differential agonist binding modes. 2011, Pubmed , Xenbase
Slimko, Codon optimization of Caenorhabditis elegans GluCl ion channel genes for mammalian cells dramatically improves expression levels. 2003, Pubmed , Xenbase
Thompson, The structural basis of function in Cys-loop receptors. 2010, Pubmed
Unwin, Refined structure of the nicotinic acetylcholine receptor at 4A resolution. 2005, Pubmed
Van Arnam, Functional probes of drug-receptor interactions implicated by structural studies: Cys-loop receptors provide a fertile testing ground. 2014, Pubmed
Xiu, Nicotine binding to brain receptors requires a strong cation-pi interaction. 2009, Pubmed , Xenbase
Xu, Identification of sequence motifs that target neuronal nicotinic receptors to dendrites and axons. 2006, Pubmed
Yakel, Single amino acid substitution affects desensitization of the 5-hydroxytryptamine type 3 receptor expressed in Xenopus oocytes. 1993, Pubmed , Xenbase
Zerangue, A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. 1999, Pubmed , Xenbase
Zhong, From ab initio quantum mechanics to molecular neurobiology: a cation-pi binding site in the nicotinic receptor. 1998, Pubmed