9K1C

Cryo-EM structure of the DHA bound FFA1-Gi complex

9K1C の概要

• エントリーDOI: 10.2210/pdb9k1c/pdb
• EMDBエントリー: 61971
• 分子名称: Free fatty acid receptor 1, Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (5 entities in total)
• 機能のキーワード: gpcr, ffar1, 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: 123724.44

構造登録者

Han, S.,Wu, B.,Zhao, Q. (登録日: 2024-10-16, 公開日: 2024-12-11)

主引用文献

Ke, Y.,Huang, Y.,Yi, C.,Ma, L.,Chu, X.,Wu, B.,Zhao, Q.,Han, S.
Structural insights into endogenous ligand selectivity and activation mechanisms of FFAR1 and FFAR2.
Cell Rep, 43:115024-115024, 2024

PubMed Abstract: Free fatty acid receptors (FFARs) play critical roles in metabolic regulation and are potential therapeutic targets for metabolic and inflammatory diseases. A comprehensive understanding of the activation mechanisms and endogenous ligand selectivity of FFARs is essential for drug discovery. Here, we report two cryoelectron microscopy structures of the human FFAR1 bound to the endogenous ligand docosahexaenoic acid (DHA) and G protein as well as FFAR2 in complex with butyrate and G at 3.2 Å and 3.3 Å resolution, respectively. These structures highlight that distinct locations and sizes of the orthosteric ligand binding pockets are crucial determinants of the endogenous ligand selectivity of this receptor subfamily. Additionally, computational analysis reveals a potential allosteric ligand binding pocket in FFAR2. Furthermore, we observe that the upward movement of helix V upon endogenous ligand binding is responsible for receptor activation. These insights will significantly aid in the development of drugs targeting this receptor family.

PubMed: 39616615
DOI: 10.1016/j.celrep.2024.115024

実験手法

ELECTRON MICROSCOPY (3.2 Å)