| Autor: |
Nguyen, Anthony H., Thomsen, Alex R. B., Cahill, Thomas J., Huang, Rick, Huang, Li-Yin, Marcink, Tara, Clarke, Oliver B., Heissel, Søren, Masoudi, Ali, Ben-Hail, Danya, Samaan, Fadi, Dandey, Venkata P., Tan, Yong Zi, Hong, Chuan, Mahoney, Jacob P., Triest, Sarah, Little, John, Chen, Xin, Sunahara, Roger, Steyaert, Jan, Molina, Henrik, Yu, Zhiheng, des Georges, Amedee, Lefkowitz, Robert J. |
| Zdroj: |
Nature Structural and Molecular Biology; December 2019, Vol. 26 Issue: 12 p1123-1131, 9p |
| Abstrakt: |
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. |
| Databáze: |
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