8JRU

Cryo-EM structure of the glucagon receptor bound to beta-arrestin 1 in ligand-free state

8JRU の概要

• エントリーDOI: 10.2210/pdb8jru/pdb
• EMDBエントリー: 36606
• 分子名称: HA signal peptide,HPC4 purification tag,Glucagon receptor,C-terminal tail of Vasopressin V2 receptor, Beta-arrestin 1 and single-chain fragment variable 30 (scFv30), Nanobody 32, ... (4 entities in total)
• 機能のキーワード: complex structure, glucagon receptor, beta-arrestin 1, ligand-free, membrane protein
• 由来する生物種: Influenza A virus (strain A/Victoria/3/1975 H3N2); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 276442.79

構造登録者

Chen, K.,Zhang, C.,Lin, S.,Zhao, Q.,Wu, B. (登録日: 2023-06-17, 公開日: 2023-08-16, 最終更新日: 2025-07-16)

主引用文献

Chen, K.,Zhang, C.,Lin, S.,Yan, X.,Cai, H.,Yi, C.,Ma, L.,Chu, X.,Liu, Y.,Zhu, Y.,Han, S.,Zhao, Q.,Wu, B.
Tail engagement of arrestin at the glucagon receptor.
Nature, 620:904-910, 2023

PubMed Abstract: Arrestins have pivotal roles in regulating G protein-coupled receptor (GPCR) signalling by desensitizing G protein activation and mediating receptor internalization. It has been proposed that the arrestin binds to the receptor in two different conformations, 'tail' and 'core', which were suggested to govern distinct processes of receptor signalling and trafficking. However, little structural information is available for the tail engagement of the arrestins. Here we report two structures of the glucagon receptor (GCGR) bound to β-arrestin 1 (βarr1) in glucagon-bound and ligand-free states. These structures reveal a receptor tail-engaged binding mode of βarr1 with many unique features, to our knowledge, not previously observed. Helix VIII, instead of the receptor core, has a major role in accommodating βarr1 by forming extensive interactions with the central crest of βarr1. The tail-binding pose is further defined by a close proximity between the βarr1 C-edge and the receptor helical bundle, and stabilized by a phosphoinositide derivative that bridges βarr1 with helices I and VIII of GCGR. Lacking any contact with the arrestin, the receptor core is in an inactive state and loosely binds to glucagon. Further functional studies suggest that the tail conformation of GCGR-βarr governs βarr recruitment at the plasma membrane and endocytosis of GCGR, and provides a molecular basis for the receptor forming a super-complex simultaneously with G protein and βarr to promote sustained signalling within endosomes. These findings extend our knowledge about the arrestin-mediated modulation of GPCR functionalities.

PubMed: 37558880
DOI: 10.1038/s41586-023-06420-x

実験手法

ELECTRON MICROSCOPY (3.5 Å)