Cryo-EM structure of small-molecule agonist bound delta opioid receptor-G_i complex enables discovery of biased compound.

ABSTRACT: Delta opioid receptor (δOR) plays a pivotal role in modulating human sensation and emotion. It is an attractive target for drug discovery since, unlike Mu opioid receptor, it is associated with low risk of drug dependence. Despite its potential applications, the pharmacological properties of δOR, including the mechanisms of activation by small-molecule agonists and the complex signaling pathways it engages, as well as their relation to the potential side effects, remain poorly understood. In this study, we use cryo-electron microscopy (cryo-EM) to determine the structure of the δOR-G_i complex when bound to a small-molecule agonist (ADL5859). Moreover, we design a series of probes to examine the key receptor-ligand interaction site and identify a region involved in signaling bias

SUBMITTER: Cheng L 

PROVIDER: S-EPMC11437176 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature