8ZBW
Cryo-EM structure of formyl peptide receptor 2/C1R receptor in complex with Gi
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Summary for 8ZBW
| Entry DOI | 10.2210/pdb8zbw/pdb |
| EMDB information | 39915 |
| Descriptor | Guanine nucleotide-binding protein G(i) subunit alpha-2, 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, ... (5 entities in total) |
| Functional Keywords | cryo-em, formyl peptide receptor 2, c1r, structural protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 117041.60 |
| Authors | |
| Primary citation | Yang, W.S.,Liu, Q.,Li, Y.,Li, G.Y.,Lin, S.,Li, J.,Li, L.Y.,Li, Y.,Ge, X.L.,Wang, X.Z.,Wu, W.,Yan, J.,Wang, G.F.,Zhou, Q.T.,Liu, Q.,Wang, M.W.,Li, Z.P. Oral FPR2/ALX modulators tune myeloid cell activity to ameliorate mucosal inflammation in inflammatory bowel disease. Acta Pharmacol.Sin., 46:1958-1973, 2025 Cited by PubMed Abstract: Current treatments of inflammatory bowel disease (IBD) largely depend on anti-inflammatory and immunosuppressive strategies with unacceptable efficacy and adverse events. Resolution or repair agents to treat IBD are not available but potential targets like formyl peptide receptor 2 (FPR2/ALX) may fill the gap. In this study we evaluated the therapeutic effects of two small molecule FPR2/ALX modulators (agonist Quin-C1 and antagonist Quin-C7) against IBD. We first analyzed the cryo-electron microscopy structure of the Quin-C1-FPR2 in complex with heterotrimeric G to reveal the structural basis for ligand recognition and FPR2 activation. We then established dextran sulfate sodium (DSS)-induced colitis model in both normal and myeloid depletion mice. We showed that oral administration of Quin-C1 for 7 days ameliorated DSS-induced colitis evidenced by alleviated disease activity indexes, reduced colonic histopathological scores, and corrected cytokine disorders. Meanwhile, we found that oral administration of FPR2/ALX antagonist Quin-C7 exerted therapeutic actions similar to those of Quin-C1. In terms of symptomatic improvements, the ED values of Quin-C1 and Quin-C7 were 1.3660 mg/kg and 2.2110 mg/kg, respectively. The underlying mechanisms involved ERK- or ERK/JNK-mediated myeloid cell regulation that limited the development of colitis and inflammation. This is the first demonstration of anti-colitis property caused by synthetic small molecule FPR2/ALX modulators, implying that FPR2/ALX modulation rather than agonism alone ameliorates IBD. PubMed: 40069490DOI: 10.1038/s41401-025-01525-7 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.58 Å) |
Structure validation
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