7F1O

Cryo-EM structure of the GDP-bound dopamine receptor 1 and mini-Gs complex with Nb35

Summary for 7F1O

• Entry DOI: 10.2210/pdb7f1o/pdb
• Related: 7F0T
• EMDB information: 31421
• Descriptor: D(1A) dopamine receptor, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short,Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (8 entities in total)
• Functional Keywords: gpcr, dopamine receptor, mini-gs, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 146422.49

Authors

Xiao, T.,Zheng, S. (deposition date: 2021-06-09, release date: 2022-06-15, Last modification date: 2024-10-30)

Primary citation

Teng, X.,Chen, S.,Wang, Q.,Chen, Z.,Wang, X.,Huang, N.,Zheng, S.
Structural insights into G protein activation by D1 dopamine receptor.
Sci Adv, 8:eabo4158-eabo4158, 2022

PubMed Abstract: G 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 complex in the nucleotide-free and nucleotide-bound states. These structures reveal major conformational changes in Gα such as structural rearrangements of the carboxyl- and amino-terminal α helices that account for the release of GDP and the GTP-dependent dissociation of Gα from Gβγ 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.

PubMed: 35687690
DOI: 10.1126/sciadv.abo4158

Experimental method

ELECTRON MICROSCOPY (3.13 Å)