9IZH

Cryo-EM structure of LPA1-G13 complex with LPA

9IZH の概要

• エントリーDOI: 10.2210/pdb9izh/pdb
• EMDBエントリー: 61033
• 分子名称: Soluble cytochrome b562,Lysophosphatidic acid receptor 1,LgBiT tag, G protein subunit 13 (Gi2-mini-G13 chimera), Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (6 entities in total)
• 機能のキーワード: gpcr, signaling protein, membrane protein
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 175980.16

構造登録者

Suzuki, S.,Nishikawa, K.,Kamegawa, A.,Hiroaki, Y.,Suzuki, H.,Fujiyoshi, Y. (登録日: 2024-08-01, 公開日: 2025-01-01, 最終更新日: 2025-06-25)

主引用文献

Suzuki, S.,Tanaka, K.,Kamegawa, A.,Nishikawa, K.,Suzuki, H.,Oshima, A.,Fujiyoshi, Y.
Structural insights into the engagement of lysophosphatidic acid receptor 1 with different G proteins.
J.Struct.Biol., 217:108164-108164, 2024

PubMed Abstract: Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are bioactive lysophospholipids derived from cell membranes that activate the endothelial differentiation gene family of G protein-coupled receptors. Activation of these receptors triggers multiple downstream signaling cascades through G proteins such as Gi/o, Gq/11, and G12/13. Therefore, LPA and S1P mediate several physiological processes, including cytoskeletal dynamics, neurite retraction, cell migration, cell proliferation, and intracellular ion fluxes. The basis for the G-protein coupling selectivity of EDG receptors, however, remains unknown. Here, we present cryo-electron microscopy structures of LPA-activated LPA1 in complexes with G, G, and G heterotrimers Comparison of the three LPA1-G protein structures shows clearly different conformations of intracellular loop 2 (ICL2) and ICL3 that are likely induced by the different Gα protein interfaces. Interestingly, this G-protein interface interaction is a common feature of LPA and S1P receptors. Our findings provide clues to understanding the promiscuity of G-protein coupling in the endothelial differentiation gene family.

PubMed: 39725093
DOI: 10.1016/j.jsb.2024.108164

実験手法

ELECTRON MICROSCOPY (3.04 Å)