{"doi":"10.3410/f.738119689.793577781","title":"Faculty Opinions recommendation of Structure of a D2 dopamine receptor-G-protein complex in a lipid membrane.","abstract":"The D 2 dopamine receptor (DRD2) is a therapeutic target for Parkinson's disease 1 and antipsychotic drugs 2 . DRD2 is activated by the endogenous neurotransmitter dopamine and synthetic agonist drugs such as bromocriptine 3 , leading to stimulation of G i and inhibition of adenylyl cyclase. 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 remodeled in response to agonist binding, with conformational changes in extracellular loop 2 (ECL2), transmembrane domain 5 (TM5), TM6, and TM7 propagating to opening of the intracellular G i binding site. The DRD2-G i structure represents the first experimental model of a GPCR-G protein complex embedded in a phospholipid bilayer, which serves as a benchmark to validate the interactions seen in previous detergent-bound structures. The structure also reveals interactions that are unique to the membrane-embedded complex, including helix 8 burial in the inner leaflet, ordered lysine and arginine sidechains in the membrane interfacial regions, and lipid anchoring of the G protein in the membrane. Our model of the activated DRD2 will help inform the design of subtype-selective DRD2 ligands for multiple human CNS disorders.","journal":"Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature","year":2020,"id":134282,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":305667,"name":"David B. Sauer","orcid":"0000-0001-9291-4640","position":1,"is_corresponding":false},{"id":305671,"name":"Da‐Neng Wang","orcid":"0000-0002-6496-4699","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T23:16:24.540681Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}