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8Y63

Cryo-EM structure of the C20:0 ceramide-bound FPR2-Gi complex

This is a non-PDB format compatible entry.
Summary for 8Y63
Entry DOI10.2210/pdb8y63/pdb
EMDB information38965
DescriptorN-formyl peptide receptor 2, Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (6 entities in total)
Functional Keywordsceramide, gpcr, membrane protein
Biological sourceHomo sapiens (human)
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Total number of polymer chains5
Total formula weight156160.57
Authors
Sun, J.P.,Jiang, C.T.,Kong, W.,Yu, X.,Cai, K.,Guo, L.L. (deposition date: 2024-02-01, release date: 2025-02-05, Last modification date: 2025-05-14)
Primary citationLin, 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
Cited by
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 FPR2 as a membrane receptor that specifically binds long-chain ceramides (C14-C20). In brown and beige adipocytes, C16:0 ceramide binding to FPR2 inhibits thermogenesis via G-cyclic AMP 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
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.2 Å)
Structure validation

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