6OMM

Cryo-EM structure of formyl peptide receptor 2/lipoxin A4 receptor in complex with Gi

Summary for 6OMM

• Entry DOI: 10.2210/pdb6omm/pdb
• EMDB information: 20126
• Descriptor: N-formyl peptide receptor 2, Peptide agonist, Guanine nucleotide-binding protein G(i) subunit alpha-1, ... (8 entities in total)
• Functional Keywords: formyl peptide receptor 2/lipoxin a4 receptor, gpcr, gi protein, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 156992.34

Authors

Zhuang, Y.,Liu, H.,de Waal, P.W.,Zhou, X.E.,Wang, L.,Meng, X.,Zhao, G.,Kang, Y.,Melcher, K.,Xu, H.E.,Zhang, C. (deposition date: 2019-04-19, release date: 2020-02-26, Last modification date: 2025-05-14)

Primary citation

Zhuang, Y.,Liu, H.,Edward Zhou, X.,Kumar Verma, R.,de Waal, P.W.,Jang, W.,Xu, T.H.,Wang, L.,Meng, X.,Zhao, G.,Kang, Y.,Melcher, K.,Fan, H.,Lambert, N.A.,Eric Xu, H.,Zhang, C.
Structure of formylpeptide receptor 2-Gicomplex reveals insights into ligand recognition and signaling.
Nat Commun, 11:885-885, 2020

PubMed Abstract: Formylpeptide receptors (FPRs) as G protein-coupled receptors (GPCRs) can recognize formylpeptides derived from pathogens or host cells to function in host defense and cell clearance. In addition, FPRs, especially FPR2, can also recognize other ligands with a large chemical diversity generated at different stages of inflammation to either promote or resolve inflammation in order to maintain a balanced inflammatory response. The mechanism underlying promiscuous ligand recognition and activation of FPRs is not clear. Here we report a cryo-EM structure of FPR2-G signaling complex with a peptide agonist. The structure reveals a widely open extracellular region with an amphiphilic environment for ligand binding. Together with computational docking and simulation, the structure suggests a molecular basis for the recognition of formylpeptides and a potential mechanism of receptor activation, and reveals conserved and divergent features in G coupling. Our results provide a basis for understanding the molecular mechanism of the functional promiscuity of FPRs.

PubMed: 32060286
DOI: 10.1038/s41467-020-14728-9

Experimental method

ELECTRON MICROSCOPY (3.17 Å)