5ZKP

Crystal structure of the human platelet-activating factor receptor in complex with SR 27417

Summary for 5ZKP

• Entry DOI: 10.2210/pdb5zkp/pdb
• Descriptor: Platelet-activating factor receptor,Flavodoxin,Platelet-activating factor receptor, N1,N1-dimethyl-N2-[(pyridin-3-yl)methyl]-N2-{4-[2,4,6-tri(propan-2-yl)phenyl]-1,3-thiazol-2-yl}ethane-1,2-diamine, FLAVIN MONONUCLEOTIDE (3 entities in total)
• Functional Keywords: g protein-coupled receptor, platelet-activating factor receptor, complex, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 1
• Total formula weight: 53351.53

Authors

Cao, C.,Zhao, Q.,Zhang, X.C.,Wu, B. (deposition date: 2018-03-25, release date: 2018-06-20, Last modification date: 2024-10-16)

Primary citation

Cao, C.,Tan, Q.,Xu, C.,He, L.,Yang, L.,Zhou, Y.,Zhou, Y.,Qiao, A.,Lu, M.,Yi, C.,Han, G.W.,Wang, X.,Li, X.,Yang, H.,Rao, Z.,Jiang, H.,Zhao, Y.,Liu, J.,Stevens, R.C.,Zhao, Q.,Zhang, X.C.,Wu, B.
Structural basis for signal recognition and transduction by platelet-activating-factor receptor.
Nat. Struct. Mol. Biol., 25:488-495, 2018

PubMed Abstract: Platelet-activating-factor receptor (PAFR) responds to platelet-activating factor (PAF), a phospholipid mediator of cell-to-cell communication that exhibits diverse physiological effects. PAFR is considered an important drug target for treating asthma, inflammation and cardiovascular diseases. Here we report crystal structures of human PAFR in complex with the antagonist SR 27417 and the inverse agonist ABT-491 at 2.8-Å and 2.9-Å resolution, respectively. The structures, supported by molecular docking of PAF, provide insights into the signal-recognition mechanisms of PAFR. The PAFR-SR 27417 structure reveals an unusual conformation showing that the intracellular tips of helices II and IV shift outward by 13 Å and 4 Å, respectively, and helix VIII adopts an inward conformation. The PAFR structures, combined with single-molecule FRET and cell-based functional assays, suggest that the conformational change in the helical bundle is ligand dependent and plays a critical role in PAFR activation, thus greatly extending knowledge about signaling by G-protein-coupled receptors.

PubMed: 29808000
DOI: 10.1038/s41594-018-0068-y

Experimental method

X-RAY DIFFRACTION (2.81 Å)