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A fungal-derived compound, ChroB, has an unanticipated mode-of-action (only two were known for GABAA targeting insecticides, since the 1950s) through a site that resembles the neurosteroid mammalian site. And nearby, a new PIP2 site.

Abamectin binds to the “classical” insecticide modulation site, where the bulk of resistant mutants are found. This -mectin bound structure is closed at the hydrophobic gate, unlike others.

The GABA-bound receptor looks so much like human receptors at the site level. Many site mutations surprisingly cause spontaneous activation. The pore helices are weirdly arranged (look at Fig. 5)

New preprint! @tatilab.bsky.social imaged the honeybee GABAA RDL receptor. ~10% of insecticides target insect GABAA receptors. She found a new allosteric modulation pocket, a PIP2 site, a closed avermectin-bound conformation, and maybe an unusual desensitized state.
www.biorxiv.org/content/10.1...