Ligand and G-protein selectivity in the κ-opioid receptor.

ABSTRACT: The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorders¹. However, the development of KOR analgesics has been hindered by the associated hallucinogenic side effects². The initiation of KOR signalling requires the G_i/o-family proteins including the conventional (G_i1, G_i2, G_i3, G_oA and G_oB) and nonconventional (G_z and G_g) subtypes. How hallucinogens exert their actions through KOR and how KOR determines G-protein subtype selectivity are not well understood. Here we determined the active-state structures of KOR in a complex with multiple G-protein heterotrimers-G_i1, G_oA, G<

SUBMITTER: Han J 

PROVIDER: S-EPMC10172140 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature