| http://purl.uniprot.org/citations/35501348 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35501348 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35501348 | http://www.w3.org/2000/01/rdf-schema#comment | "GPR88 is an orphan class A G-protein-coupled receptor that is highly expressed in the striatum and regulates diverse brain and behavioral functions. Here we present cryo-EM structures of the human GPR88-Gi1 signaling complex with or without a synthetic agonist (1R, 2R)-2-PCCA. We show that (1R, 2R)-2-PCCA is an allosteric modulator binding to a herein identified pocket formed by the cytoplasmic ends of transmembrane segments 5, 6, and the extreme C terminus of the α5 helix of Gi1. We also identify an electron density in the extracellular orthosteric site that may represent a putative endogenous ligand of GPR88. These structures, together with mutagenesis studies and an inactive state model obtained from metadynamics simulations, reveal a unique activation mechanism for GPR88 with a set of distinctive structure features and a water-mediated polar network. Overall, our results provide a structural framework for understanding the ligand binding, activation and signaling mechanism of GPR88, and will facilitate the innovative drug discovery for neuropsychiatric disorders and for deorphanization of this receptor."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41467-022-30081-5"xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41467-022-30081-5"xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Chen G."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Chen G."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Du Y."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Du Y."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Liu Z."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Liu Z."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Lu Q."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Lu Q."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Inoue A."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Inoue A."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Xu J."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Xu J."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Bai C."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Bai C."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Gmeiner P."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Gmeiner P."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Schmidt M.F."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/author | "Schmidt M.F."xsd:string |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35501348 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |