8Y62

Cryo-EM structure of the C16:0 ceramide-bound FPR2-Gi complex

8Y62 の概要

• エントリーDOI: 10.2210/pdb8y62/pdb
• EMDBエントリー: 38964
• 分子名称: Guanine nucleotide-binding protein G(i) subunit alpha-1, 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, ... (6 entities in total)
• 機能のキーワード: 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: 156231.56

構造登録者

Sun, J.P.,Jiang, C.T.,Kong, W.,Yu, X.,Cai, K.,Guo, L.L. (登録日: 2024-02-01, 公開日: 2025-02-05, 最終更新日: 2025-06-25)

主引用文献

Lin, H.,Ma, C.,Cai, K.,Guo, L.,Wang, X.,Lv, L.,Zhang, C.,Lin, J.,Zhang, D.,Ye, C.,Wang, T.,Huang, S.,Han, J.,Zhang, Z.,Gao, J.,Zhang, M.,Pu, Z.,Li, F.,Guo, Y.,Zhou, X.,Qin, C.,Yi, F.,Yu, X.,Kong, W.,Jiang, C.,Sun, J.P.
Metabolic signaling of ceramides through the FPR2 receptor inhibits adipocyte thermogenesis.
Science, 388:eado4188-eado4188, 2025

PubMed Abstract: Ceramides play a central role in human health and disease, yet their role as systemic signaling molecules remain poorly understood. In this work, we identify formyl peptide receptor 2 (FPR2) as a membrane receptor that specifically binds long-chain ceramides (C14 to C20). In brown and beige adipocytes, C16:0 ceramide binding to FPR2 inhibits thermogenesis through G cyclic adenosine monophosphate signaling pathways, an effect that is reversed in the absence of FPR2. We present three cryo-electron microscopy structures of FPR2 in complex with G trimers bound to C16:0, C18:0, and C20:0 ceramides. The hydrophobic tails are deeply embedded in the orthosteric ligand pocket, which has a limited amount of plasticity. Modification of the ceramide binding motif in closely related receptors, such as FPR1 or FPR3, converts them from inactive to active ceramide receptors. Our findings provide a structural basis for adipocyte thermogenesis mediated by FPR2.

PubMed: 40080544
DOI: 10.1126/science.ado4188

実験手法

ELECTRON MICROSCOPY (3.2 Å)