7T6T
Structure of the human FPR1-Gi complex with fMLFII
Summary for 7T6T
| Entry DOI | 10.2210/pdb7t6t/pdb |
| EMDB information | 25727 |
| Descriptor | 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) |
| Functional Keywords | gpcr, membrane protein, signaling protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 126986.48 |
| Authors | Zhuang, Y.W. (deposition date: 2021-12-14, release date: 2022-03-30, Last modification date: 2024-10-23) |
| Primary citation | Zhuang, Y.,Wang, L.,Guo, J.,Sun, D.,Wang, Y.,Liu, W.,Xu, H.E.,Zhang, C. Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2. Nat Commun, 13:1054-1054, 2022 Cited by PubMed Abstract: The formylpeptide receptors (FPRs) mediate pattern recognition of formylated peptides derived from invading pathogens or mitochondria from dead host cells. They can also sense other structurally distinct native peptides and even lipid mediators to either promote or resolve inflammation. Pharmacological targeting of FPRs represents a novel therapeutic approach in treating inflammatory diseases. However, the molecular mechanisms underlying FPR ligand recognition are elusive. We report cryo-EM structures of G-coupled FPR1 and FPR2 bound to a formylpeptide and G-coupled FPR2 bound to two synthetic peptide and small-molecule agonists. Together with mutagenesis data, our structures reveal the molecular mechanism of formylpeptide recognition by FPRs and structural variations of FPR1 and FPR2 leading to their different ligand preferences. Structural analysis also suggests that diverse FPR agonists sample a conserved activation chamber at the bottom of ligand-binding pockets to activate FPRs. Our results provide a basis for rational drug design on FPRs. PubMed: 35217703DOI: 10.1038/s41467-022-28586-0 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
Download full validation report
