Activation-Induced Conformational Changes of Dopamine D3 Receptor Promote the Formation of the Internal Water Channel.

ABSTRACT: The atomic-level dopamine activation mechanism for transmitting extracellular ligand binding events through transmembrane helices to the cytoplasmic G protein remains unclear. In the present study, the complete dopamine D3 receptor (D3R), with a homology-modeled N-terminus, was constructed to dock different ligands to simulate conformational alterations in the receptor's active and inactive forms during microsecond-timescale molecular dynamic simulations. In agonist-bound systems, the D3R N-terminus formed a "lid-like" structure and lay flat on the binding site opening, whereas in antagonist and inverse agonist-bound systems, the N-terminus exposed the binding cavity. Receptor activation was characterized using the different molecular switch residue distances, and G protein-binding site vo

SUBMITTER: Weng WH 

PROVIDER: S-EPMC5630584 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature