Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41594-019-0330-y
Title: Structure of an endosomal signaling GPCR-G protein-beta-arrestin megacomplex
Authors: Nguyen, Anthony H
Thomsen, Alex RB
Cahill, Thomas J
Huang, Rick
Huang, Li-Yin
Marcink, Tara
Clarke, Oliver B
Heissel, Soren
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
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biophysics
Cell Biology
CRYO-EM STRUCTURE
CRYSTAL-STRUCTURE
COUPLED RECEPTOR
PEPTIDE IDENTIFICATION
GLP-1 RECEPTOR
COMPLEX
VISUALIZATION
RESOLUTION
DESENSITIZATION
BETA-ARRESTIN1
Issue Date: 1-Dec-2019
Publisher: NATURE PUBLISHING GROUP
Citation: Nguyen, Anthony H, Thomsen, Alex RB, Cahill, Thomas J, Huang, Rick, Huang, Li-Yin, Marcink, Tara, Clarke, Oliver B, Heissel, Soren, 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 (2019-12-01). Structure of an endosomal signaling GPCR-G protein-beta-arrestin megacomplex. NATURE STRUCTURAL & MOLECULAR BIOLOGY 26 (12) : 1123-+. ScholarBank@NUS Repository. https://doi.org/10.1038/s41594-019-0330-y
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.
Source Title: NATURE STRUCTURAL & MOLECULAR BIOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/227206
ISSN: 15459993
15459985
DOI: 10.1038/s41594-019-0330-y
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