Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane.

ABSTRACT: The D2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease¹ and antipsychotic drugs². DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such as bromocriptine³, leading to stimulation of G_i and inhibition of adenylyl cyclase. Here we used cryo-electron microscopy to elucidate the structure of an agonist-bound activated DRD2-G_i complex reconstituted into a phospholipid membrane. The extracellular ligand-binding site of DRD2 is remodelled in response to agonist binding, with conformational changes in extracellular loop 2, transmembrane domain 5 (TM5), TM6 and TM7, propagating to opening of the intracellular G_i-binding site. The DRD2-G_i structure represents,

SUBMITTER: Yin J 

PROVIDER: S-EPMC7415663 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature