EMD-9376

Single-particle
3.8 Å
EMD-9376 Deposition: 26/12/2018
Map released: 20/11/2019
Last modified: 16/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-9376

B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin mega-complex

EMD-9376

Single-particle
3.8 Å
EMD-9376 Deposition: 26/12/2018
Map released: 20/11/2019
Last modified: 16/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Lama glama
Sample: B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin mega-complex
Fitted models: 6ni3 (Avg. Q-score: 0.39)

Deposition Authors: Nguyen AH , Thomsen ARB
Structure of an endosomal signaling GPCR-G protein-beta-arrestin megacomplex.
PUBMED: 31740855
DOI: doi:10.1038/s41594-019-0330-y
ISSN: 1545-9985
Abstract:
Classically, G-protein-coupled receptors (GPCRs) are thought to activate G protein from the plasma membrane and are subsequently desensitized by β-arrestin (β-arr). However, some GPCRs continue to signal through G protein from internalized compartments, mediated by a GPCR-G protein-β-arr 'megaplex'. Nevertheless, the molecular architecture of the megaplex remains unknown. Here, we present its cryo-electron microscopy structure, which shows simultaneous engagement of human G protein and bovine β-arr to the core and phosphorylated tail, respectively, of a single active human chimeric β2-adrenergic receptor with the C-terminal tail of the arginine vasopressin type 2 receptor (β2V2R). All three components adopt their canonical active conformations, suggesting that a single megaplex GPCR is capable of simultaneously activating G protein and β-arr. Our findings provide a structural basis for GPCR-mediated sustained internalized G protein signaling.