Mechanistic insights into dopaminergic and serotonergic neurotransmission - concerted interactions with helices 5 and 6 drive the functional outcome.

ABSTRACT: Brain functions rely on neurotransmitters that mediate communication between billions of neurons. Disruption of this communication can result in a plethora of psychiatric and neurological disorders. In this work, we combine molecular dynamics simulations, live-cell biosensor and electrophysiological assays to investigate the action of the neurotransmitter dopamine at the dopaminergic D₂ receptor (D₂R). The study of dopamine and closely related chemical probes reveals how neurotransmitter binding translates into the activation of distinct subsets of D₂R effectors (i.e.: G_i2, G_oB, G_z and β-arrestin 2). Ligand interactions with key residues in TM5 (S5.42) and TM6 (H6.55) in the D₂R binding pocket yield a dopam

SUBMITTER: Stepniewski TM 

PROVIDER: S-EPMC8386650 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature