8JSR

Cryo-EM structure of the anamorelin-bound ghrelin receptor and Gq complex

8JSR の概要

• エントリーDOI: 10.2210/pdb8jsr/pdb
• EMDBエントリー: 36627
• 分子名称: Growth hormone secretagogue receptor type 1, Engineered G-alpha-q, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (7 entities in total)
• 機能のキーワード: gpcr, sbdd, cachexia, 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: 193042.94

構造登録者

Im, D.,Shiimura, Y.,Asada, H.,Iwata, S. (登録日: 2023-06-20, 公開日: 2025-01-22, 最終更新日: 2025-12-10)

主引用文献

Shiimura, Y.,Im, D.,Tany, R.,Asada, H.,Kise, R.,Kurumiya, E.,Wakasugi-Masuho, H.,Yasuda, S.,Matsui, K.,Kishikawa, J.I.,Kato, T.,Murata, T.,Kojima, M.,Iwata, S.,Masuho, I.
The structure and function of the ghrelin receptor coding for drug actions.
Nat.Struct.Mol.Biol., 32:531-542, 2025

PubMed Abstract: Drugs targeting the ghrelin receptor hold therapeutic potential in anorexia, obesity and diabetes. However, developing effective drugs is challenging. To tackle this common issue across a broad drug target, this study aims to understand how anamorelin, the only approved drug targeting the ghrelin receptor, operates compared to other synthetic drugs. Our research elucidated the receptor's structure with anamorelin and miniG, unveiling anamorelin's superagonistic activity. We demonstrated that ligands with distinct chemical structures uniquely bind to the receptor, resulting in diverse conformations and biasing signal transduction. Moreover, our study showcased the utility of structural information in effectively identifying natural genetic variations altering drug action and causing severe functional deficiencies, offering a basis for selecting the right medication on the basis of the individual's genomic sequence. Thus, by building on structural analysis, this study enhances the foundational framework for selecting therapeutic agents targeting the ghrelin receptor, by effectively leveraging signaling bias and genetic variations.

PubMed: 39833471
DOI: 10.1038/s41594-024-01481-6

実験手法

ELECTRON MICROSCOPY (2.9 Å)