6NI2

Stabilized beta-arrestin 1-V2T subcomplex of a GPCR-G protein-beta-arrestin mega-complex

Summary for 6NI2

• Entry DOI: 10.2210/pdb6ni2/pdb
• EMDB information: 9375 9376 9377
• Descriptor: Nanobody 32, Beta-arrestin-1, Fab30 Heavy Chain, ... (5 entities in total)
• Functional Keywords: arrestin, gpcr signaling transducer, scaffolding protein, signaling protein-immune system complex, signaling protein/immune system
• Biological source: Lama glama (Llama); More
• Total number of polymer chains: 5
• Total formula weight: 110037.85

Authors

Nguyen, A.H.,Thomsen, A.R.B.,Cahill, T.J.,des Georges, A.,Lefkowitz, R.J. (deposition date: 2018-12-26, release date: 2019-11-20, Last modification date: 2024-11-20)

Primary citation

Nguyen, A.H.,Thomsen, A.R.B.,Cahill 3rd, T.J.,Huang, R.,Huang, L.Y.,Marcink, T.,Clarke, O.B.,Heissel, S.,Masoudi, A.,Ben-Hail, D.,Samaan, F.,Dandey, V.P.,Tan, Y.Z.,Hong, C.,Mahoney, J.P.,Triest, S.,Little 4th, J.,Chen, X.,Sunahara, R.,Steyaert, J.,Molina, H.,Yu, Z.,des Georges, A.,Lefkowitz, R.J.
Structure of an endosomal signaling GPCR-G protein-beta-arrestin megacomplex.
Nat.Struct.Mol.Biol., 26:1123-1131, 2019

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 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.

PubMed: 31740855
DOI: 10.1038/s41594-019-0330-y

Experimental method

ELECTRON MICROSCOPY (4 Å)