Dopamine receptor D2

5AER181313489ENSG00000149295ENSMUSG00000032259P14416P61168NM_016574NM_000795NM_010077NP_000786NP_057658NP_000786.1NP_034207Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups (including those of Solomon Snyder and Philip Seeman) used a radiolabeled antipsychotic drug to identify what is now known as the dopamine D2 receptor. The dopamine D2 receptor is the main receptor for most antipsychotic drugs. The structure of DRD2 in complex with the atypical antipsychotic risperidone has been determined. Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups (including those of Solomon Snyder and Philip Seeman) used a radiolabeled antipsychotic drug to identify what is now known as the dopamine D2 receptor. The dopamine D2 receptor is the main receptor for most antipsychotic drugs. The structure of DRD2 in complex with the atypical antipsychotic risperidone has been determined. This gene encodes the D2 subtype of the dopamine receptor, which is coupled to Gi subtype of G protein-coupled receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity. In mice, regulation of D2R surface expression by the neuronal calcium sensor-1 (NCS-1) in the dentate gyrus is involved in exploration, synaptic plasticity and memory formation. A recent study has shown a potential role for D2R in retrieval of fear memories in the prelimbic cortex. In flies, activation of the D2 autoreceptor protected dopamine neurons from cell death induced by MPP+, a toxin mimicking Parkinson's disease pathology. While optimal dopamine levels favor D1R cognitive stabilization, it is the D2R that mediates the cognitive flexibility in humans. Alternative splicing of this gene results in three transcript variants encoding different isoforms. The long form (D2Lh) has the 'canonical' sequence and functions as a classic post-synaptic receptor. The short form (D2Sh) is pre-synaptic and functions as an autoreceptor that regulates the levels of dopamine in the synaptic cleft. Agonism of D2sh receptors inhibits dopamine release; antagonism increases dopaminergic release. A third D2(Longer) form differs from the canonical sequence where 270V is replaced by VVQ. D2R conformers are equilibrated between two full active (D2HighR) and inactive (D2LowR) states, while in complex with an agonist and antagonist ligand, respectively. The monomeric inactive conformer of D2R in binding with Risperidone was reported in 2018 (PDB ID: 6CM4). However, the active form which is generally bound to an agonist, is not available yet and in most of the studies the Homology modeling of the structure is implemented. The difference between the active and inactive of G protein-coupled receptor is mainly observed as conformational changes at the cytoplasmic half of the structure, particularly at the transmembrane domains (TM) 5 and 6. The conformational transitions occurred at the cytoplasmic ends are due to the coupling of G protein to the cytoplasmic loop between the TM 5 and 6.