EMD-9376
B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin mega-complex
EMD-9376
Single-particle3.8 Å
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Map released: 20/11/2019
Last modified: 16/10/2024
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
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
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Structure of an endosomal signaling GPCR-G protein-beta-arrestin megacomplex.
Nguyen AH
,
Thomsen ARB
,
Cahill 3rd TJ,
Huang R,
Huang LY,
Marcink T
,
Clarke OB,
Heissel S,
Masoudi A,
Ben-Hail D
,
Samaan F
,
Dandey VP,
Tan YZ
,
Hong C,
Mahoney JP
,
Triest S
,
Little 4th J
,
Chen X
,
Sunahara R
,
Steyaert J
,
Molina H,
Yu Z,
des Georges A
,
Lefkowitz RJ
(2019) Nat Struct Mol Biol , 26 , 1123 - 1131
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(2019) Nat Struct Mol Biol , 26 , 1123 - 1131
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.
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.