DREADDs (Designer Receptors Exclusively Activated by a Designer Drug) represent a powerful chemogenetic technology for remotely controlling neuronal activity and cellular signaling.   I will report four DREADD-related cryoEM high-resolution structures, including two deschloroclozapine (DCZ) bound to the hM3Dq-miniGq and hM4Di-miniGo complexes, a clozapine-N-oxide (CNO)-bound hM3Dq-miniGq complex, and an iperoxo-bound hM3R-miniGq complex. Complemented with mutagenesis, functional, and computational simulation data, our structures reveal key details of DREADD chemogenetic actuators' recognition and the molecular basis for activation. I will also show how these findings accelerate the design of new chemogenetic actuators and receptors.

Chemogenetics: How structural insights accelerate new chemogenetic tools

Where thousands of chemistry professionals meet to share ideas and advance scientific and technical knowledge. Spring 2023 abstracts, posters, and presentations will launch at the end of March.

ACS Spring 2023

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.