7WY0

GPR110/G13 complex

7WY0 の概要

• エントリーDOI: 10.2210/pdb7wy0/pdb
• EMDBエントリー: 32883
• 分子名称: Engineered G alpha 13 subunit, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, scFv16, ... (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: 214724.40

構造登録者

He, Y.,Zhu, X. (登録日: 2022-02-15, 公開日: 2022-09-28, 最終更新日: 2024-10-09)

主引用文献

Zhu, X.,Qian, Y.,Li, X.,Xu, Z.,Xia, R.,Wang, N.,Liang, J.,Yin, H.,Zhang, A.,Guo, C.,Wang, G.,He, Y.
Structural basis of adhesion GPCR GPR110 activation by stalk peptide and G-proteins coupling.
Nat Commun, 13:5513-5513, 2022

PubMed Abstract: Adhesion G protein-coupled receptors (aGPCRs) are keys of many physiological events and attractive targets for various diseases. aGPCRs are also known to be capable of self-activation via an autoproteolysis process that removes the inhibitory GAIN domain on the extracellular side of receptor and releases a stalk peptide to bind and activate the transmembrane side of receptor. However, the detailed mechanism of aGPCR activation remains elusive. Here, we report the cryo-electron microscopy structures of GPR110 (ADGRF1), a member of aGPCR, in complex with G, G, G, G and G The structures reveal distinctive ligand engaging model and activation conformations of GPR110. The structures also unveil the rarely explored GPCR/G and GPCR/G engagements. A comparison of G, G, G, G and G engagements with GPR110 reveals details of G-protein engagement, including a dividing point at the far end of the alpha helix 5 (αH5) of Gα subunit that separates G/G engagements from G/G/G engagements. This is also where G/G bind the receptor through both hydrophobic and polar interaction, while G/G/G engage receptor mainly through hydrophobic interaction. We further provide physiological evidence of GPR110 activation via stalk peptide. Taken together, our study fills the missing information of GPCR/G-protein engagement and provides a framework for understanding aGPCR activation and GPR110 signaling.

PubMed: 36127364
DOI: 10.1038/s41467-022-33173-4

実験手法

ELECTRON MICROSCOPY (2.83 Å)