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 DOI | 10.2210/pdb8y63/pdb |
EMDB information | 38965 |
Descriptor | N-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 Keywords | ceramide, gpcr, membrane protein |
Biological source | Homo sapiens (human) More |
Total number of polymer chains | 5 |
Total formula weight | 156160.57 |
Authors | |
Primary citation | 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 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: 40080544DOI: 10.1126/science.ado4188 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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