7XZ6

GPR119-Gs-APD668 complex

7XZ6 の概要

• エントリーDOI: 10.2210/pdb7xz6/pdb
• EMDBエントリー: 33526
• 分子名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, 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, ... (7 entities in total)
• 機能のキーワード: gpcr, glucose-dependent insulinotropic receptor, gpr119, lysopc, lysophosphatidylcholine, apd668, g-protein, gs, signaling complex, cryo-em structure, structure-function relationships, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 161010.65

構造登録者

Xu, P.,Huang, S.,Jiang, Y.,Xu, H.E. (登録日: 2022-06-02, 公開日: 2022-08-24, 最終更新日: 2024-11-20)

主引用文献

Xu, P.,Huang, S.,Guo, S.,Yun, Y.,Cheng, X.,He, X.,Cai, P.,Lan, Y.,Zhou, H.,Jiang, H.,Jiang, Y.,Xie, X.,Xu, H.E.
Structural identification of lysophosphatidylcholines as activating ligands for orphan receptor GPR119.
Nat.Struct.Mol.Biol., 29:863-870, 2022

PubMed Abstract: Lysophosphatidylcholine (LPC) is an essential mediator in human lipid metabolism and is associated with a variety of diseases, but the exact identity of LPC receptors remains controversial. Through extensive biochemical and structural analyses, we have identified the orphan receptor GPR119 as the receptor for LPC. The structure of the GPR119-G-protein complex without any added ligands reveals a density map that fits well with LPC, which is further confirmed by mass spectrometry and functional studies. As LPCs are abundant on the cell membrane, their preoccupancy in the receptor may lead to 'constitutive activity' of GPR119. The structure of GPR119 bound to APD668, a clinical drug candidate for type 2 diabetes, reveals an exceedingly similar binding mode to LPC. Together, these data highlight structural evidence for LPC function in regulating glucose-dependent insulin secretion through direct binding and activation of GPR119, and provide structural templates for drug design targeting GPR119.

PubMed: 35970999
DOI: 10.1038/s41594-022-00816-5

実験手法

ELECTRON MICROSCOPY (2.8 Å)