7EUO

The structure of formyl peptide receptor 1 in complex with Gi and peptide agonist fMLF

Summary for 7EUO

• Entry DOI: 10.2210/pdb7euo/pdb
• EMDB information: 31323
• Descriptor: fMet-Leu-Phe receptor, Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (7 entities in total)
• Functional Keywords: formyl peptide receptor 1, gi complex, signaling protein, signaling protein-immune system complex, signaling protein/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 159470.87

Authors

Wang, X.K.,Chen, G.,Liao, Q.W.,Du, Y.,Hu, H.L.,Ye, D.Q. (deposition date: 2021-05-18, release date: 2022-05-25, Last modification date: 2022-12-07)

Primary citation

Chen, G.,Wang, X.,Liao, Q.,Ge, Y.,Jiao, H.,Chen, Q.,Liu, Y.,Lyu, W.,Zhu, L.,van Zundert, G.C.P.,Robertson, M.J.,Skiniotis, G.,Du, Y.,Hu, H.,Ye, R.D.
Structural basis for recognition of N-formyl peptides as pathogen-associated molecular patterns.
Nat Commun, 13:5232-5232, 2022

PubMed Abstract: The formyl peptide receptor 1 (FPR1) is primarily responsible for detection of short peptides bearing N-formylated methionine (fMet) that are characteristic of protein synthesis in bacteria and mitochondria. As a result, FPR1 is critical to phagocyte migration and activation in bacterial infection, tissue injury and inflammation. How FPR1 distinguishes between formyl peptides and non-formyl peptides remains elusive. Here we report cryo-EM structures of human FPR1-Gi protein complex bound to S. aureus-derived peptide fMet-Ile-Phe-Leu (fMIFL) and E. coli-derived peptide fMet-Leu-Phe (fMLF). Both structures of FPR1 adopt an active conformation and exhibit a binding pocket containing the R201XXXR205 (RGIIR) motif for formyl group interaction and receptor activation. This motif works together with D106 for hydrogen bond formation with the N-formyl group and with fMet, a model supported by MD simulation and functional assays of mutant receptors with key residues for recognition substituted by alanine. The cryo-EM model of agonist-bound FPR1 provides a structural basis for recognition of bacteria-derived chemotactic peptides with potential applications in developing FPR1-targeting agents.

PubMed: 36064945
DOI: 10.1038/s41467-022-32822-y

Experimental method

ELECTRON MICROSCOPY (2.9 Å)