Home
Resources
Publications
Structure of an Endosomal Signaling GPCR-G protein-β-arrestin Megacomplex

Structure of an Endosomal Signaling GPCR-G protein-β-arrestin Megacomplex

Anthony H Nguyen, Alex R B Thomsen, Thomas J Cahill 3rd, 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, etc.

Nat Struct Mol Biol. 2019 Dec;26(12):1123-1131.

PMID: 31740855

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42417921	RPTPg Active human			Price
IAR4245700	PDE4A1A Active human			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: