Insect antennae, palps, labellae and tarsi contain neurons expressing ionotropic chemoreceptors (Irs). Irs are ligand-gated ion channels and are thus functionally similar to insect olfactory receptors (Ors) and gustatory receptors (Grs). However, the receptor structures are completely different: Irs are related to the ionotropic glutamate receptor (iGluR) protein family, and Ors and Grs belong to the 7TMIC protein family. We previously examined 7TMIC structures and found that transiently opening tunnels to the occluded ligand binding sites may filter ligands by molecular size and flexibility. This filtering could exclude repellents from binding to attractant receptors. By contrast, the ligand binding sites in Irs are located in an open groove in the ligand-binding domain (LBD). After ligand binding, the LBD undergoes a large conformational change that causes the groove to close around the ligand, and this triggers opening of the ion channel. I have now examined the docking of repellents to molecular models of both the open and closed conformations of Ir LBDs. The models were obtained from artificial intellegence software that produces high quality structures. Repellent binding was examined in Irs known to have behavioral responses of attraction or aversion in the vinegar fly, Drosophila melanogaster. Repellent binding was also studied in Irs known to be expressed in the fore tarsi of the black-legged tick, Ixodes scapularis. LBDs from iGluRs that are expressed separately from the receptor ion channel are known to stably bind to their ligands. Therefore, modeling studies could help the design of high throughput repellent screening assays.
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