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-Structure paper
タイトル | Structure of an endosomal signaling GPCR-G protein-β-arrestin megacomplex. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 26, Issue 12, Page 1123-1131, Year 2019 |
掲載日 | 2019年11月18日 |
著者 | Anthony H Nguyen / Alex R B Thomsen / Thomas J Cahill / 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 / Chuan Hong / Jacob P Mahoney / Sarah Triest / John Little / Xin Chen / Roger Sunahara / Jan Steyaert / Henrik Molina / Zhiheng Yu / Amedee des Georges / Robert J Lefkowitz / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:31740855 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.8 - 4.84 Å |
構造データ | EMDB-9375, PDB-6ni2: EMDB-9376, PDB-6ni3: EMDB-9377: |
化合物 | ChemComp-P0G: |
由来 |
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キーワード | SIGNALING PROTEIN/IMMUNE SYSTEM / arrestin (アレスチン) / GPCR signaling transducer / scaffolding protein (足場タンパク質) / SIGNALING PROTEIN-IMMUNE SYSTEM complex / GPCR (Gタンパク質共役受容体) / Gs protein (Gsタンパク質αサブユニット) / signaling transducer |