8XWP

Cryo-EM structure of ET-1 bound ETBR-DNGI complex

8XWP の概要

• エントリーDOI: 10.2210/pdb8xwp/pdb
• EMDBエントリー: 38740
• 分子名称: Endothelin receptor type B, Endothelin-1, Guanine nucleotide-binding protein G(i) subunit alpha-1, ... (6 entities in total)
• 機能のキーワード: endothelin, receptor, gi, complex, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 156651.43

構造登録者

Tani, K.,Maki-Yonekura, S.,Kanno, R.,Negami, T.,Hamaguchi, T.,Hall, M.,Mizoguchi, A.,Humbel, B.M.,Terada, T.,Yonekura, K.,Doi, T. (登録日: 2024-01-16, 公開日: 2024-10-02, 最終更新日: 2024-10-30)

主引用文献

Tani, K.,Maki-Yonekura, S.,Kanno, R.,Negami, T.,Hamaguchi, T.,Hall, M.,Mizoguchi, A.,Humbel, B.M.,Terada, T.,Yonekura, K.,Doi, T.
Structure of endothelin ET B receptor-G i complex in a conformation stabilized by unique NPxxL motif.
Commun Biol, 7:1303-1303, 2024

PubMed Abstract: Endothelin type B receptor (ETR) plays a crucial role in regulating blood pressure and humoral homeostasis, making it an important therapeutic target for related diseases. ETR activation by the endogenous peptide hormones endothelin (ET)-1-3 stimulates several signaling pathways, including G, G, G, G, and β-arrestin. Although the conserved NPxxY motif in transmembrane helix 7 (TM7) is important during GPCR activation, ETR possesses the lesser known NPxxL motif. In this study, we present the cryo-EM structure of the ETR-G complex, complemented by MD simulations and functional studies. These investigations reveal an unusual movement of TM7 to the intracellular side during ETR activation and the essential roles of the diverse NPxxL motif in stabilizing the active conformation of ETR and organizing the assembly of the binding pocket for the α5 helix of G protein. These findings enhance our understanding of the interactions between GPCRs and G proteins, thereby advancing the development of therapeutic strategies.

PubMed: 39414992
DOI: 10.1038/s42003-024-06905-z

実験手法

ELECTRON MICROSCOPY (3.21 Å)