Affiliation:
1. Department of Anesthesiology Washington University School of Medicine St. Louis MO USA
2. Center for Clinical Pharmacology University of Health Sciences & Pharmacy and Washington University School of Medicine St. Louis MO USA
Abstract
Receptor‐G protein promiscuity is frequently observed in class A G protein‐coupled receptors (GPCRs). In particular, GPCRs can couple with G proteins from different families (Gαs, Gαq/11, Gαi/o, and Gα12/13) or the same family subtypes. The molecular basis underlying the selectivity/promiscuity is not fully revealed. We recently reported the structures of kappa opioid receptor (KOR) in complex with the Gi/o family subtypes [Gαi1, GαoA, Gαz, and Gustducin (Gαg)] determined by cryo‐electron microscopy (cryo‐EM). The structural analysis, in combination with pharmacological studies, provides insights into Gi/o subtype selectivity. Given the conserved sequence identity and activation mechanism between different G protein families, the findings within Gi/o subtypes could be likely extended to other families. Understanding the KOR‐Gi/o or GPCR‐G protein selectivity will facilitate the development of more precise therapeutics targeting a specific G protein subtype.
Funder
National Institute of General Medical Sciences
Subject
Cell Biology,Molecular Biology,Biochemistry