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Cryo-EM structure of the GDP-bound dopamine receptor 1 and mini-Gs complex with Nb35Cryo-EM structure of the GDP-bound dopamine receptor 1 and mini-Gs complex with Nb35
Structural highlights
FunctionGBB1_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.[1] Publication Abstract from PubMedG protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors and are the most important drug targets. An agonist-bound GPCR engages heterotrimeric G proteins and triggers the exchange of guanosine diphosphate (GDP) with guanosine triphosphate (GTP) to promote G protein activation. A complete understanding of molecular mechanisms of G protein activation has been hindered by a lack of structural information of GPCR-G protein complex in nucleotide-bound states. Here, we report the cryo-EM structures of the D1 dopamine receptor and mini-G(s) complex in the nucleotide-free and nucleotide-bound states. These structures reveal major conformational changes in Galpha such as structural rearrangements of the carboxyl- and amino-terminal alpha helices that account for the release of GDP and the GTP-dependent dissociation of Galpha from Gbetagamma subunits. As validated by biochemical and cellular signaling studies, our structures shed light into the molecular basis of the entire signaling events of GPCR-mediated G protein activation. Structural insights into G protein activation by D1 dopamine receptor.,Teng X, Chen S, Wang Q, Chen Z, Wang X, Huang N, Zheng S Sci Adv. 2022 Jun 10;8(23):eabo4158. doi: 10.1126/sciadv.abo4158. Epub 2022 Jun , 10. PMID:35687690[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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