+Search query
-Structure paper
Title | Structure of an endosomal signaling GPCR-G protein-β-arrestin megacomplex. |
---|---|
Journal, issue, pages | Nat Struct Mol Biol, Vol. 26, Issue 12, Page 1123-1131, Year 2019 |
Publish date | Nov 18, 2019 |
Authors | Anthony H Nguyen / Alex R B Thomsen / Thomas J Cahill / Rick Huang / Li-Yin Huang / Tara Marcink / Oliver B Clarke / Søren Heissel / Ali Masoudi / Danya Ben-Hail / Fadi Samaan / Venkata P Dandey / Yong Zi Tan / Chuan Hong / Jacob P Mahoney / Sarah Triest / John Little / Xin Chen / Roger Sunahara / Jan Steyaert / Henrik Molina / Zhiheng Yu / Amedee des Georges / Robert J Lefkowitz / |
PubMed 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 ...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 β-adrenergic receptor with the C-terminal tail of the arginine vasopressin type 2 receptor (βVR). 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. |
External links | Nat Struct Mol Biol / PubMed:31740855 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.8 - 4.84 Å |
Structure data | EMDB-9375, PDB-6ni2: EMDB-9376, PDB-6ni3: EMDB-9377: |
Chemicals | ChemComp-P0G: |
Source |
|
Keywords | SIGNALING PROTEIN/IMMUNE SYSTEM / arrestin / GPCR signaling transducer / scaffolding protein / SIGNALING PROTEIN-IMMUNE SYSTEM complex / GPCR / Gs protein / signaling transducer |