8JMT

Structure of the adhesion GPCR ADGRL3 in the apo state

8JMT の概要

• エントリーDOI: 10.2210/pdb8jmt/pdb
• EMDBエントリー: 36426
• 分子名称: Adhesion G protein-coupled receptor L3,Soluble cytochrome b562 (1 entity in total)
• 機能のキーワード: adgrl3, apo form, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 85439.92

構造登録者

Tao, Y.,Guo, Q.,He, B.,Zhong, Y. (登録日: 2023-06-05, 公開日: 2023-09-06, 最終更新日: 2025-07-02)

主引用文献

Guo, Q.,He, B.,Zhong, Y.,Jiao, H.,Ren, Y.,Wang, Q.,Ge, Q.,Gao, Y.,Liu, X.,Du, Y.,Hu, H.,Tao, Y.
A method for structure determination of GPCRs in various states.
Nat.Chem.Biol., 20:74-82, 2024

PubMed Abstract: G-protein-coupled receptors (GPCRs) are a class of integral membrane proteins that detect environmental cues and trigger cellular responses. Deciphering the functional states of GPCRs induced by various ligands has been one of the primary goals in the field. Here we developed an effective universal method for GPCR cryo-electron microscopy structure determination without the need to prepare GPCR-signaling protein complexes. Using this method, we successfully solved the structures of the β-adrenergic receptor (βAR) bound to antagonistic and agonistic ligands and the adhesion GPCR ADGRL3 in the apo state. For βAR, an intermediate state stabilized by the partial agonist was captured. For ADGRL3, the structure revealed that inactive ADGRL3 adopts a compact fold and that large unusual conformational changes on both the extracellular and intracellular sides are required for activation of adhesion GPCRs. We anticipate that this method will open a new avenue for understanding GPCR structure‒function relationships and drug development.

PubMed: 37580554
DOI: 10.1038/s41589-023-01389-0

実験手法

ELECTRON MICROSCOPY (3.36 Å)