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TitleStructural insights into G protein activation by D1 dopamine receptor.
Journal, issue, pagesSci Adv, Vol. 8, Issue 23, Page eabo4158, Year 2022
Publish dateJun 10, 2022
AuthorsXiao Teng / Sijia Chen / Qing Wang / Zhao Chen / Xiaoying Wang / Niu Huang / Sanduo Zheng /
PubMed AbstractG 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 ...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.
External linksSci Adv / PubMed:35687690 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 4.16 Å
Structure data

EMDB-31404, PDB-7f0t:
Cryo-EM structure of dopamine receptor 1 and mini-Gs complex with dopamine bound
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-31421, PDB-7f1o:
Cryo-EM structure of the GDP-bound dopamine receptor 1 and mini-Gs complex with Nb35
Method: EM (single particle) / Resolution: 3.13 Å

EMDB-31425, PDB-7f1z:
Cryo-EM structure of the GDP-bound dopamine receptor 1 and mini-Gs complex without Nb35
Method: EM (single particle) / Resolution: 3.46 Å

EMDB-31426, PDB-7f23:
Cryo-EM structure of the GTP-bound dopamine receptor 1 and mini-Gs complex with Nb35
Method: EM (single particle) / Resolution: 3.58 Å

EMDB-31427, PDB-7f24:
Cryo-EM structure of the GTP-bound dopamine receptor 1 and mini-Gs complex without Nb35
Method: EM (single particle) / Resolution: 4.16 Å

Chemicals

ChemComp-LDP:
L-DOPAMINE / medication*YM

ChemComp-MG:
Unknown entry

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsMEMBRANE PROTEIN / GPCR / dopamine receptor / mini-Gs

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