7WY5

ADGRL3/Gq complex

7WY5 の概要

• エントリーDOI: 10.2210/pdb7wy5/pdb
• EMDBエントリー: 32884
• 分子名称: engineered mini G alpha q subunit, 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, ... (5 entities in total)
• 機能のキーワード: gpcr, membrane protein
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 277058.43

構造登録者

He, Y.,Qian, Y. (登録日: 2022-02-15, 公開日: 2022-10-26, 最終更新日: 2024-11-20)

主引用文献

Qian, Y.,Ma, Z.,Liu, C.,Li, X.,Zhu, X.,Wang, N.,Xu, Z.,Xia, R.,Liang, J.,Duan, Y.,Yin, H.,Xiong, Y.,Zhang, A.,Guo, C.,Chen, Z.,Huang, Z.,He, Y.
Structural insights into adhesion GPCR ADGRL3 activation and Gq, Gs, Gi, and G12 coupling.
Mol.Cell, 82:4340-4352.e6, 2022

PubMed Abstract: Adhesion G-protein-coupled receptors (aGPCRs) play key roles in a diversity of physiologies. A hallmark of aGPCR activation is the removal of the inhibitory GAIN domain and the dipping of the cleaved stalk peptide into the ligand-binding pocket of receptors; however, the detailed mechanism remains obscure. Here, we present cryoelectron microscopy (cryo-EM) structures of ADGRL3 in complex with G, G, G, and G. The structures reveal unique ligand-engaging mode, distinctive activation conformation, and key mechanisms of aGPCR activation. The structures also reveal the uncharted structural information of GPCR/G coupling. A comparison of G, G, G, and G engagements with ADGRL3 reveals the key determinant of G-protein coupling on the far end of αH5 of Gα. A detailed analysis of the engagements allows us to design mutations that specifically enhance one pathway over others. Taken together, our study lays the groundwork for understanding aGPCR activation and G-protein-coupling selectivity.

PubMed: 36309016
DOI: 10.1016/j.molcel.2022.10.009

実験手法

ELECTRON MICROSCOPY (2.83 Å)