7WU5

Cryo-EM structure of the adhesion GPCR ADGRF1(H565A/T567A) in complex with miniGi

7WU5 の概要

• エントリーDOI: 10.2210/pdb7wu5/pdb
• EMDBエントリー: 32820
• 分子名称: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• 機能のキーワード: adhesion gpcr, adgrf1, g protein, complex, signal transduction, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 149565.57

構造登録者

Qu, X.,Qiu, N.,Wang, M.,Zhao, Q.,Wu, B. (登録日: 2022-02-05, 公開日: 2022-04-27, 最終更新日: 2024-10-16)

主引用文献

Qu, X.,Qiu, N.,Wang, M.,Zhang, B.,Du, J.,Zhong, Z.,Xu, W.,Chu, X.,Ma, L.,Yi, C.,Han, S.,Shui, W.,Zhao, Q.,Wu, B.
Structural basis of tethered agonism of the adhesion GPCRs ADGRD1 and ADGRF1.
Nature, 604:779-785, 2022

PubMed Abstract: Adhesion G protein-coupled receptors (aGPCRs) are essential for a variety of physiological processes such as immune responses, organ development, cellular communication, proliferation and homeostasis. An intrinsic manner of activation that involves a tethered agonist in the N-terminal region of the receptor has been proposed for the aGPCRs, but its molecular mechanism remains elusive. Here we report the G protein-bound structures of ADGRD1 and ADGRF1, which exhibit many unique features with regard to the tethered agonism. The stalk region that proceeds the first transmembrane helix acts as the tethered agonist by forming extensive interactions with the transmembrane domain; these interactions are mostly conserved in ADGRD1 and ADGRF1, suggesting that a common stalk-transmembrane domain interaction pattern is shared by members of the aGPCR family. A similar stalk binding mode is observed in the structure of autoproteolysis-deficient ADGRF1, supporting a cleavage-independent manner of receptor activation. The stalk-induced activation is facilitated by a cascade of inter-helix interaction cores that are conserved in positions but show sequence variability in these two aGPCRs. Furthermore, the intracellular region of ADGRF1 contains a specific lipid-binding site, which proves to be functionally important and may serve as the recognition site for the previously discovered endogenous ADGRF1 ligand synaptamide. These findings highlight the diversity and complexity of the signal transduction mechanisms of the aGPCRs.

PubMed: 35418679
DOI: 10.1038/s41586-022-04580-w

実験手法

ELECTRON MICROSCOPY (3 Å)