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-Structure paper
Title | Structural insights into G protein activation by D1 dopamine receptor. |
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Journal, issue, pages | Sci Adv, Vol. 8, Issue 23, Page eabo4158, Year 2022 |
Publish date | Jun 10, 2022 |
Authors | Xiao Teng / Sijia Chen / Qing Wang / Zhao Chen / Xiaoying Wang / Niu Huang / Sanduo Zheng / |
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 ...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 links | Sci Adv / PubMed:35687690 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.1 - 4.16 Å |
Structure data | EMDB-31404, PDB-7f0t: EMDB-31421, PDB-7f1o: EMDB-31425, PDB-7f1z: EMDB-31426, PDB-7f23: EMDB-31427, PDB-7f24: |
Chemicals | ChemComp-LDP: ChemComp-MG: ChemComp-GDP: ChemComp-GTP: |
Source |
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Keywords | MEMBRANE PROTEIN / GPCR / dopamine receptor / mini-Gs |